The physiology of protein s-acylation

Physiological Reviews

Volumn 95, Issue 2, 2015, Pages 341-376

  Chamberlain, Luke H ^a,b   Shipston, Michael J ^a,b  

^a UNIVERSITY OF STRATHCLYDE   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; ION CHANNEL; MEMBRANE PROTEIN; MEMBRANE RECEPTOR; THIOL ESTER HYDROLASE; PALMITIC ACID; PROTEIN;

ACYLATION; ARTICLE; CELL ADHESION; HUMAN; MEMBRANE BINDING; NONHUMAN; PHYSIOLOGY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN SECRETION; PROTEIN TRANSPORT; PROTEOMICS; REGULATORY MECHANISM; ANIMAL; CHEMISTRY; METABOLISM; PROCEDURES; PROTEIN CONFORMATION; PROTEIN PROCESSING; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

ACYLATION; ANIMALS; HUMANS; PALMITIC ACID; PROTEIN CONFORMATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEINS; PROTEOMICS; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84926624340     PISSN: 00319333     EISSN: 15221210     Source Type: Journal    
DOI: 10.1152/physrev.00032.2014     Document Type: Article

References (294)

1. Abrami L, Kunz B, Iacovache I, van der Goot FG. Palmitoylation and ubiquitination regulate exit of the Wnt signaling protein LRP6 from the endoplasmic reticulum. Proc Natl Acad Sci USA 105: 5384–5389, 2008
2. Abrami L, Leppla SH, der Goot van FG. Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis. J Cell Biol 172: 309–320, 2006
3. Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Hodder PS, Rosen H, Cravatt BF. Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes. J Am Chem Soc 134: 10345–10348, 2012
4. Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessières E, Kim SH, Lière P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, Lenfant F. Mutation of the palmitoylation site of estrogen receptor a in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci USA 111: E283–E290, 2014
5. Ahearn IM, Haigis K, Bar-Sagi D, Philips MR. Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol 13: 39–51, 2012
6. Ahearn IM, Tsai FD, Court H, Zhou M, Jennings BC, Ahmed M, Fehrenbacher N, Linder ME, Philips MR. FKBP12 binds to acylated H-ras and promotes depalmitoylation. Mol Cell 41: 173–185, 2011
7. Aikawa Y, Lynch KL, Boswell KL, Martin TFJ. A second SNARE role for exocytic SNAP25 in endosome fusion. Mol Biol Cell 17: 2113–2124, 2006
8. Aitken A, Cohen P, Santikarn S, Williams DH, Calder AG, Smith A, Klee CB. Identification of the NH2-terminal blocking group of calcineurin B as myristic acid. FEBS Lett 150: 314–318, 1982
9. Aittaleb M, Nishimura A, Linder ME, Tesmer JJG. Plasma membrane association of p63 Rho guanine nucleotide exchange factor (p63RhoGEF) is mediated by palmitoylation and is required for basal activity in cells. J Biol Chem 286: 34448–34456, 2011
10. Akerström S, Gunalan V, Keng CT, Tan YJ, Mirazimi A. Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected. Virology 395: 1–9, 2009
11. Anami K, Oue N, Noguchi T, Sakamoto N, Sentani K, Hayashi T, Hinoi T, Okajima M, Graff JM, Yasui W. Search for transmembrane protein in gastric cancer by the Escherichia coli ampicillin secretion trap: expression of DSC2 in gastric cancer with intestinal phenotype. J Pathol 221: 275–284, 2010
12. Bachovchin DA, Ji T, Li W, Simon GM, Blankman JL, Adibekian A, Hoover H, Niessen S, Cravatt BF. Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening. Proc Natl Acad Sci USA 107: 20941–20946, 2010
13. Baker TL, Booden MA, Buss JE. S-nitrosocysteine increases palmitate turnover on Ha-Ras in NIH 3T3 cells. J Biol Chem 275: 22037–22047, 2000
14. Bartels DJ, Mitchell DA, Dong X, Deschenes RJ. Erf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae. Mol Cell Biol 19: 6775–6787, 1999
15. Barylko B, Mao YS, Wlodarski P, Jung G, Binns DD, Sun HQ, Yin HL, Albanesi JP. Palmitoylation controls the catalytic activity and subcellular distribution of phosphatidylinositol 4-kinase IIa. J Biol Chem 284: 9994–10003, 2009
16. Birkenkamp-Demtroder K, Christensen LL, Olesen SH, Frederiksen CM, Laiho P, Aaltonen LA, Laurberg S, Sørensen FB, Hagemann R, ØRntoft TF. Gene expression in colorectal cancer. Cancer Res 62: 4352–4363, 2002
17. Botham A, Guo X, Xiao YP, Morice AH, Compton SJ, Sadofsky LR. Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signaling and endocytosis. Biochem J 438: 359–367, 2011
18. Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347: 768–770, 1990
19. Brigidi GS, Sun Y, Beccano-Kelly D, Pitman K, Mobasser M, Borgland SL, Milnerwood AJ, Bamji SX. Palmitoylation of d-catenin by DHHC5 mediates activity-induced synapse plasticity. Nat Neurosci 17: 522–532, 2014
20. Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 275: 17221–17224, 2000
21. Buglino JA, Resh MD. Palmitoylation of hedgehog proteins. Vitam Horm 88: 229–252, 2012
22. Burgoyne JR, Haeussler DJ, Kumar V, Ji Y, Pimental DR, Zee RS, Costello CE, Lin C, McComb ME, Cohen RA, Bachschmid MM. Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis. FASEB J 26: 832–841, 2012
23. Camp LA, Hofmann SL. Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J Biol Chem 268: 22566–22574, 1993
24. Camp LA, Verkruyse LA, Afendis SJ, Slaughter CA, Hofmann SL. Molecular cloning and expression of palmitoyl-protein thioesterase. J Biol Chem 269: 23212–23219, 1994
25. Carr SA, Biemann K, Shoji S, Parmelee DC, Titani K. n-Tetradecanoyl is the NH2- terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle. Proc Natl Acad Sci USA 79: 6128–6131, 1982
26. Casey PJ. Biochemistry of protein prenylation. J Lipid Res 33: 1731–1740, 1992
27. Chai S, Cambronne XA, Eichhorn SW, Goodman RH. MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9. Proc Natl Acad Sci USA 110: 17898–17903, 2013
28. Chang SC, Magee AI. Acyltransferases for secreted signalling proteins (Review). Mol Membr Biol 26: 104–113, 2009
29. Charest PG, Bouvier M. Palmitoylation of the V2 vasopressin receptor carboxyl tail enhances beta-arrestin recruitment leading to efficient receptor endocytosis and ERK1/2 activation. J Biol Chem 278: 41541–41551, 2003
30. Charron G, Wilson J, Hang HC. Chemical tools for understanding protein lipidation in eukaryotes. Curr Opin Chem Biol 13: 382–391, 2009
31. Charron G, Zhang MM, Yount JS, Wilson J, Raghavan AS, Shamir E, Hang HC. Robust fluorescent detection of protein fatty-acylation with chemical reporters. J Am Chem Soc 131: 4967–4975, 2009
32. Charych EI, Jiang LX, Lo F, Sullivan K, Brandon NJ. Interplay of palmitoylation and phosphorylation in the trafficking and localization of phosphodiesterase 10A: implications for the treatment of schizophrenia. J Neurosci 30: 9027–9037, 2010
33. Chen L, Bi D, Tian L, Mcclafferty H, Steeb F, Ruth P, Knaus HG, Shipston MJ. Palmitoylation of the β4-subunit regulates surface expression of large conductance calciumactivated potassium channel splice variants. J Biol Chem 288:13136–13144, 2013
34. Chen X, Du Z, Shi W, Wang C, Yang Y, Wang F, Yao Y, He K, Hao A. 2-Bromopalmitate modulates neuronal differentiation through the regulation of histone acetylation. Stem Cell Res 12: 481–491, 2014
35. Cheng H, Vetrivel KS, Drisdel RC, Meckler X, Gong P, Leem JY, Li T, Carter M, Chen Y, Nguyen P, Iwatsubo T, Tomita T, Wong PC, Green WN, Kounnas MZ, Thinakaran G. S-palmitoylation of gamma-secretase subunits nicastrin and APH-1. J Biol Chem 284: 1373–1384, 2009
36. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318: 1258–1265, 2007
37. Chini B, Parenti M. G-protein-coupled receptors, cholesterol and palmitoylation: facts about fats. J Mol Endocrinol 42: 371–379, 2009
38. Craven SE, El-Husseini AE, Bredt DS. Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs. Neuron 22: 497–509, 1999
39. Davda D, Azzouny El MA, Tom CTMB, Hernandez JL, Majmudar JD, Kennedy RT, Martin BR. Profiling targets of the irreversible palmitoylation inhibitor 2-bromopalmitate. ACS Chem Biol 8: 1912–1917, 2013
40. Dekker FJ, Rocks O, Vartak N, Menninger S, Hedberg C, Balamurugan R, Wetzel S, Renner S, Gerauer M, Schölermann B, Rusch M, Kramer JW, Rauh D, Coates GW, Brunsveld L, Bastiaens PIH, Waldmann H. Small-molecule inhibition of APT1 affects Ras localization and signaling. Nat Chem Biol 6: 449–456, 2010
41. Delint-Ramirez I, Willoughby D, Hammond GVR, Ayling LJ, Cooper DMF. Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calciumsensitive adenylyl cyclase type 8. J Biol Chem 286: 32962–32975, 2011
42. Dighe SA, Kozminski KG. Swf1p, a member of the DHHC-CRD family of palmitoyltransferases, regulates the actin cytoskeleton and polarized secretion independently of its DHHC motif. Mol Biol Cell 19: 4454–4468, 2008
43. Draper JM, Smith CD. Palmitoyl acyltransferase assays and inhibitors (Review). Mol Membr Biol 26: 5–13, 2009
44. Drisdel RC, Alexander JK, Sayeed A, Green WN. Assays of protein palmitoylation. Methods 40: 127–134, 2006
45. Drisdel RC, Green WN. Labeling and quantifying sites of protein palmitoylation. BioTechniques 36: 276–285, 2004
46. Ducker CE, Griffel LK, Smith RA, Keller SN, Zhuang Y, Xia Z, Diller JD, Smith CD. Discovery and characterization of inhibitors of human palmitoyl acyltransferases. Mol Cancer Ther 5: 1647–1659, 2006
47. Dumaresq-Doiron K, Jules F, Lefrancois S. Sortilin turnover is mediated by ubiquitination. Biochem Biophys Res Commun 433: 90–95, 2013
48. Duncan JA, Gilman AG. A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). J Biol Chem 273: 15830–15837, 1998
49. Eggeling C, Ringemann C, Medda R, Schwarzmann G, Sandhoff K, Polyakova S, Belov VN, Hein B, Middendorff von C, Schönle A, Hell SW. Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457: 1159–1162, 2009
50. Eisenhaber B, Sammer M, Lua WH, Benetka W, Liew LL, Yu W, Lee HK, Koranda M, Eisenhaber F, Adhikari S. Nuclear import of a lipid-modified transcription factor: mobilization of NFAT5 isoform a by osmotic stress. Cell Cycle 10: 3897–3911, 2011
51. El-Husseini AED, Bredt DS. Protein palmitoylation: a regulator of neuronal development and function. Nat Rev Neurosci 3: 791–802, 2002
52. El-Husseini AED, Schnell E, Dakoji S, Sweeney N, Zhou Q, Prange O, Gauthier- Campbell C, Aguilera-Moreno A, Nicoll RA, Bredt DS. Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108: 849–863, 2002
53. Emmer BT, Nakayasu ES, Souther C, Choi H, Sobreira TJP, Epting CL, Nesvizhskii AI, Almeida IC, Engman DM. Global analysis of protein palmitoylation in African trypanosomes. Eukaryotic Cell 10: 455–463, 2011
54. Fernández-Hernando C, Fukata M, Bernatchez PN, Fukata Y, Lin MI, Bredt DS, Sessa WC. Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase. J Cell Biol 174: 369–377, 2006
55. Flannery AR, Czibener C, Andrews NW. Palmitoylation-dependent association with CD63 targets the Ca2+ sensor synaptotagmin VII to lysosomes. J Cell Biol 191: 599–613, 2010
56. Forrester MT, Hess DT, Thompson JW, Hultman R, Moseley MA, Stamler JS, Casey PJ. Site-specific analysis of protein S-acylation by resin-assisted capture. J Lipid Res 52: 393–398, 2011
57. Foster JD, Vaughan RA. Palmitoylation controls dopamine transporter kinetics, degradation, and protein kinase C-dependent regulation. J Biol Chem 286: 5175–5186, 2011
58. Fraser ID, Tavalin SJ, Lester LB, Langeberg LK, Westphal AM, Dean RA, Marrion NV, Scott JD. A novel lipid-anchored A-kinase anchoring protein facilitates cAMP-responsive membrane events. EMBO J 17: 2261–2272, 1998
59. Frénal K, Kemp LE, Soldati-Favre D. Emerging roles for protein S-palmitoylation in Toxoplasma biology. Int J Parasitol 44: 121–131, 2014
60. Fujita M, Kinoshita T. Structural remodeling of GPI anchors during biosynthesis and after attachment to proteins. FEBS Lett 584: 1670–1677, 2010
61. Fukata M, Fukata Y, Adesnik H, Nicoll RA, Bredt DS. Identification of PSD-95 palmitoylating enzymes. Neuron 44: 987–996, 2004
62. Fukata Y, Dimitrov A, Boncompain G, Vielemeyer O, Perez F, Fukata M. Local palmitoylation cycles define activity-regulated postsynaptic subdomains. J Cell Biol 202: 145–161, 2013
63. Gao X, Hannoush RN. Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine. Nat Chem Biol 10: 61–68, 2014
64. García-Cardeña G, Oh P, Liu J, Schnitzer JE, Sessa WC. Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci USA 93: 6448–6453, 1996
65. Giglione C, Boularot A, Meinnel T. Protein N-terminal methionine excision. Cell Mol Life Sci 61: 1455–1474, 2004
66. Goldston AM, Sharma AI, Paul KS, Engman DM. Acylation in trypanosomatids: an essential process and potential drug target. Trends Parasitol 30: 350–360, 2014
67. González Montoro A, Chumpen Ramirez S, Quiroga R, Valdez Taubas J. Specificity of transmembrane protein palmitoylation in yeast. PLoS One 6: e16969, 2011
68. Gorleku OA, Barns AM, Prescott GR, Greaves J, Chamberlain LH. Endoplasmic reticulum localization of DHHC palmitoyltransferases mediated by lysine-based sorting signals. J Biol Chem 286: 39573–39584, 2011
69. Goytain A, Hines RM, Quamme GA. Huntingtin-interacting proteins, HIP14 and HIP14L, mediate dual functions, palmitoyl acyltransferase and Mg2+ transport. J Biol Chem 283: 33365–33374, 2008
70. Gray PC, Johnson BD, Westenbroek RE, Hays LG, Yates JR, Scheuer T, Catterall WA, Murphy BJ. Primary structure and function of an A kinase anchoring protein associated with calcium channels. Neuron 20: 1017–1026, 1998
71. Greaves J, Carmichael JA, Chamberlain LH. The palmitoyl transferaseDHHC2targets a dynamic membrane cycling pathway: regulation by a C-terminal domain. Mol Biol Cell 22: 1887–1895, 2011
72. Greaves J, Chamberlain LH. Palmitoylation-dependent protein sorting. J Cell Biol 176: 249–254, 2007
73. Greaves J, Chamberlain LH. Differential palmitoylation regulates intracellular patterning of SNAP25. J Cell Sci 124: 1351–1360, 2011
74. Greaves J, Chamberlain LH. DHHC palmitoyl transferases: substrate interactions and (patho)physiology. Trends Biochem Sci 36: 245–253, 2011
75. Greaves J, Gorleku OA, Salaun C, Chamberlain LH. Palmitoylation of the SNAP25 protein family: specificity and regulation by DHHC palmitoyl transferases. J Biol Chem 285: 24629–24638, 2010
76. Greaves J, Lemonidis K, Gorleku OA, Cruchaga C, Grefen C, Chamberlain LH. Palmitoylation- induced aggregation of cysteine-string protein mutants that cause neuronal ceroid lipofuscinosis. J Biol Chem 287: 37330–37339, 2012
77. Greaves J, Prescott GR, Fukata Y, Fukata M, Salaun C, Chamberlain LH. The hydrophobic cysteine-rich domain of SNAP25 couples with downstream residues to mediate membrane interactions and recognition by DHHC palmitoyl transferases. Mol Biol Cell 20: 1845–1854, 2009
78. Greaves J, Salaun C, Fukata Y, Fukata M, Chamberlain LH. Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein. J Biol Chem 283: 25014–25026, 2008
79. Gu HM, Li G, Gao X, Berthiaume LG, Zhang DW. Characterization of palmitoylation of ATP binding cassette transporter G1: effect on protein trafficking and function. Biochim Biophys Acta 1831: 1067–1078, 2013
80. Hancock JF, Cadwallader K, Paterson H, Marshall CJ. A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins. EMBO J 10: 4033–4039, 1991
81. Hancock JF, Magee AI, Childs JE, Marshall CJ. All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57: 1167–1177, 1989
82. Hancock JF, Paterson H, Marshall CJ. A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell 63: 133–139, 1990
83. Hannoush RN, Arenas-Ramirez N. Imaging the lipidome: omega-alkynyl fatty acids for detection and cellular visualization of lipid-modified proteins. ACS Chem Biol 4: 581–587, 2009
84. Hannoush RN, Sun J. The chemical toolbox for monitoring protein fatty acylation and prenylation. Nat Chem Biol 6: 498–506, 2010
85. Hannoush RN. Profiling cellular myristoylation and palmitoylation using_-alkynyl fatty acids. Methods Mol Biol 800: 85–94, 2012
86. Hayashi T, Rumbaugh G, Huganir RL. Differential regulation of AMPA receptor subunit trafficking by palmitoylation of two distinct sites. Neuron 47: 709–723, 2005
87. Hayashi T, Thomas GM, Huganir RL. Dual palmitoylation of NR2 subunits regulates NMDA receptor trafficking. Neuron 64: 213–226, 2009
88. He M, Abdi KM, Bennett V. Ankyrin-G palmitoylation and II-spectrin binding to phosphoinositide lipids drive lateral membrane assembly. J Cell Biol 206: 273–288, 2014
89. He M, Jenkins P, Bennett V. Cysteine 70 of ankyrin-G is S-palmitoylated and is required for function of ankyrin-G in membrane domain assembly. J Biol Chem 287: 43995–44005, 2012
90. He Y, Linder ME. Differential palmitoylation of the endosomal SNAREs syntaxin 7 and syntaxin 8. J Lipid Res 50: 398–404, 2009
91. Heal WP, Jovanovic B, Bessin S, Wright MH, Magee AI, Tate EW. Bioorthogonal chemical tagging of protein cholesterylation in living cells. Chem Commun 47: 4081–4083, 2011
92. Hellewell AL, Foresti O, Gover N, Porter MY, Hewitt EW. Analysis of familial hemophagocytic lymphohistiocytosis type 4 (FHL-4) mutant proteins reveals that S-acylation is required for the function of syntaxin 11 in natural killer cells. PLoS One 9: e98900, 2014
93. Hellsten E, Vesa J, Olkkonen VM, Jalanko A, Peltonen L. Human palmitoyl protein thioesterase: evidence for lysosomal targeting of the enzyme and disturbed cellular routing in infantile neuronal ceroid lipofuscinosis. EMBO J 15: 5240–5245, 1996
94. Hemsley PA, Grierson CS. The ankyrin repeats and DHHC S-acyl transferase domain of AKR1 act independently to regulate switching from vegetative to mating states in yeast. PLoS One 6: e28799, 2011
95. Hemsley PA, Weimar T, Lilley KS, Dupree P, Grierson CS. A proteomic approach identifies many novel palmitoylated proteins in Arabidopsis. New Phytol 197: 805–814, 2013
96. Hemsley PA. Protein S-acylation in plants (Review). Mol Membr Biol 26: 114–125, 2009
97. Hess DT, Patterson SI, Smith DS, Skene JH. Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide. Nature 366: 562–565, 1993
98. Hess DT, Slater TM, Wilson MC, Skene JH. The 25 kDa synaptosomal-associated protein SNAP-25 is the major methionine-rich polypeptide in rapid axonal transport and a major substrate for palmitoylation in adult CNS. J Neurosci 12: 4634–4641, 1992
99. Hérincs Z, Corset V, Cahuzac N, Furne C, Castellani V, Hueber AO, Mehlen P. DCC association with lipid rafts is required for netrin-1-mediated axon guidance. J Cell Sci 118: 1687–1692, 2005
100. Hilgemann DW, Fine M, Linder ME, Jennings BC, Lin MJ. Massive endocytosis triggered by surface membrane palmitoylation under mitochondrial control in BHK fibroblasts. Elife 2: e01293, 2013
101. Hines RM, Kang R, Goytain A, Quamme GA. Golgi-specific DHHC zinc finger protein GODZ mediates membrane Ca2+ transport. J Biol Chem 285: 4621–4628, 2010
102. Ho GPH, Selvakumar B, Mukai J, Hester LD, Wang Y, Gogos JA, Snyder SH. Snitrosylation and S-palmitoylation reciprocally regulate synaptic targeting of PSD-95. Neuron 71: 131–141, 2011
103. Horstmeyer A, Cramer H, Sauer T, Müller-Esterl W, Schroeder C. Palmitoylation of endothelin receptor A. Differential modulation of signal transduction activity by posttranslational modification. J Biol Chem 271: 20811–20819, 1996
104. Hou H, John Peter AT, Meiringer C, Subramanian K, Ungermann C. Analysis of DHHC acyltransferases implies overlapping substrate specificity and a two-step reaction mechanism. Traffic 10: 1061–1073, 2009
105. Huang K, Sanders S, Singaraja R, Orban P, Cijsouw T, Arstikaitis P, Yanai A, Hayden MR, El-Husseini A. Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity. FASEB J 23: 2605–2615, 2009
106. Huang K, Sanders SS, Kang R, Carroll JB, Sutton L, Wan J, Singaraja R, Young FB, Liu L, El-Husseini A, Davis NG, Hayden MR. Wild-type HTT modulates the enzymatic activity of the neuronal palmitoyl transferase HIP14. Hum Mol Genet 20: 3356–3365, 2011
107. Huang K, Yanai A, Kang R, Arstikaitis P, Singaraja RR, Metzler M, Mullard A, Haigh B, Gauthier-Campbell C, Gutekunst CA, Hayden MR, El-Husseini A. Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Neuron 44: 977–986, 2004
108. Ivaldi C, Martin BR, Kieffer-Jaquinod S, Chapel A, Levade T, Garin J, Journet A. Proteomic analysis of S-acylated proteins in human B cells reveals palmitoylation of the immune regulators CD20 and CD23. PLoS One 7: e37187, 2012
109. Iwanaga T, Tsutsumi R, Noritake J, Fukata Y, Fukata M. Dynamic protein palmitoylation in cellular signaling. Prog Lipid Res 48: 117–127, 2009
110. Jeffries O, Geiger N, Rowe ICM, Tian L, McClafferty H, Chen L, Bi D, Knaus HG, Ruth P, Shipston MJ. Palmitoylation of the S0–S1 linker regulates cell surface expression of voltage- and calcium-activated potassium (BK) channels. J Biol Chem 285: 33307–33314, 2010
111. Jeffries O, Tian L, McClafferty H, Shipston MJ. An electrostatic switch controls palmitoylation of the large conductance voltage- and calcium-activated potassium (BK) channel. J Biol Chem 287: 1468–1477, 2012
112. Jennings BC, Linder ME. DHHC protein S-acyltransferases use similar ping-pong kinetic mechanisms but display different acyl-CoA specificities. J Biol Chem 287: 7236–7245, 2012
113. Jennings BC, Nadolski MJ, Ling Y, Baker MB, Harrison ML, Deschenes RJ, Linder ME. 2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one inhibit DHHC-mediated palmitoylation in vitro. J Lipid Res 50: 233–242, 2009
114. Ji Y, Leymarie N, Haeussler DJ, Bachschmid MM, Costello CE, Lin C. Direct detection of s-palmitoylation by mass spectrometry. Anal Chem 85: 11952–11959, 2013
115. Jia L, Chisari M, Maktabi MH, Sobieski C, Zhou H, Konopko AM, Martin BR, Mennerick SJ, Blumer KJ. A mechanism regulating G protein-coupled receptor signaling that requires cycles of protein palmitoylation and depalmitoylation. J Biol Chem 289: 6249–6257, 2014
116. Jia L, Linder ME, Blumer KJ. Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7 family-binding protein. J Biol Chem 286: 13695–13703, 2011
117. Jiang X, Benovic JL, Wedegaertner PB. Plasma membrane and nuclear localization of G protein coupled receptor kinase 6A. Mol Biol Cell 18: 2960–2969, 2007
118. Jones ML, Collins MO, Goulding D, Choudhary JS, Rayner JC. Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis. Cell Host Microbe 12: 246–258, 2012
119. Kalyanaraman H, Schwappacher R, Joshua J, Zhuang S, Scott BT, Klos M, Casteel DE, Frangos JA, Dillmann W, Boss GR, Pilz RB. Nongenomic thyroid hormone signaling occurs through a plasma membrane-localized receptor. Sci Signal 7: ra48, 2014
120. Kang JU, Koo SH, Kwon KC, Park JW, Kim JM. Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic event in early stages of non-small cell lung cancer. Cancer Genet Cytogenet 182: 1–11, 2008
121. Kang R, Swayze R, Lise MF, Gerrow K, Mullard A, Honer WG, El-Husseini A. Presynaptic trafficking of synaptotagmin I is regulated by protein palmitoylation. J Biol Chem 279: 50524–50536, 2004
122. Kang R, Wan J, Arstikaitis P, Takahashi H, Huang K, Bailey AO, Thompson JX, Roth AF, Drisdel RC, Mastro R, Green WN, Yates JR, Davis NG, El-Husseini A. Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature 456: 904–909, 2008
123. Keith DJ, Sanderson JL, Gibson ES, Woolfrey KM, Robertson HR, Olszewski K, Kang R, El-Husseini A, Dell’Acqua ML. Palmitoylation of A-kinase anchoring protein 79/150 regulates dendritic endosomal targeting and synaptic plasticity mechanisms. J Neurosci 32: 7119–7136, 2012
124. Keller CA, Yuan X, Panzanelli P, Martin ML, Alldred M, Sassoè-Pognetto M, Lüscher B. The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation by GODZ. J Neurosci 24: 5881–5891, 2004
125. King MJ, Sharma RK. Demonstration of multiple forms of bovine brain myristoyl CoA:protein N-myristoyl transferase. Mol Cell Biochem 113: 77–81, 1992
126. Kinlough CL, McMahan RJ, Poland PA, Bruns JB, Harkleroad KL, Stremple RJ, Kashlan OB, Weixel KM, Weisz OA, Hughey RP. Recycling of MUC1 is dependent on its palmitoylation. J Biol Chem 281: 12112–12122, 2006
127. Koegl M, Zlatkine P, Ley SC, Courtneidge SA, Magee AI. Palmitoylation of multiple Src-family kinases at a homologous N-terminal motif. Biochem J 303: 749–753, 1994
128. Kordyukova LV, Serebryakova MV, Baratova LA, Veit M. S-acylation of the hemagglutinin of influenza viruses: mass spectrometry reveals site-specific attachment of stearic acid to a transmembrane cysteine. J Virol 82: 9288–9292, 2008
129. Kordyukova LV, Serebryakova MV, Baratova LA, Veit M. Site-specific attachment of palmitate or stearate to cytoplasmic versus transmembrane cysteines is a common feature of viral spike proteins. Virology 398: 49–56, 2010
130. La Rosa P, Pesiri V, Leclercq G, Marino M, Acconcia F. Palmitoylation regulates 17β-estradiol-induced estrogen receptor-a degradation and transcriptional activity. Mol Endocrinol 26: 762–774, 2012
131. Lai J, Linder ME. Oligomerization of DHHC protein S-acyltransferases. J Biol Chem 288: 22862–22870, 2013
132. Lakkaraju AK, Abrami L, Lemmin T, Blaskovic S, Kunz B, Kihara A, Dal Peraro M, van der Goot FG. Palmitoylated calnexin is a key component of the ribosome-translocon complex. EMBO J 31: 1823–1835, 2012
133. Lam KKY, Davey M, Sun B, Roth AF, Davis NG, Conibear E. Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3. J Cell Biol 174: 19–25, 2006
134. Lane KT, Beese LS. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res 47: 681–699, 2006
135. Leung KF, Baron R, Seabra MC. Thematic review series: lipid posttranslational modifications. Geranylgeranylation of Rab GTPases. J Lipid Res 47: 467–475, 2006
136. Levental I, Grzybek M, Simons K. Greasing their way: lipid modifications determine protein association with membrane rafts. Biochemistry 49: 6305–6316, 2010
137. Levental I, Lingwood D, Grzybek M, Coskun U, Simons K. Palmitoylation regulates raft affinity for the majority of integral raft proteins. Proc Natl Acad Sci USA 107: 22050–22054, 2010
138. Li Y, Hu J, Höfer K, Wong AMS, Cooper JD, Birnbaum SG, Hammer RE, Hofmann SL. DHHC5 interacts with PDZ domain 3 of post-synaptic density-95 (PSD-95) protein and plays a role in learning and memory. J Biol Chem 285: 13022–13031, 2010
139. Li Y, Martin BR, Cravatt BF, Hofmann SL. DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on induction of neuronal differentiation in cultured cells. J Biol Chem 287: 523–530, 2012
140. Liang X, Nazarian A, Erdjument-Bromage H, Bornmann W, Tempst P, Resh MD. Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction. J Biol Chem 276: 30987–30994, 2001
141. Lichtenberg D, Goñi FM, Heerklotz H. Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem Sci 30: 430–436, 2005
142. Lin DT, Makino Y, Sharma K, Hayashi T, Neve R, Takamiya K, Huganir RL. Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation. Nat Neurosci 12: 879–887, 2009
143. Lin MJ, Fine M, Lu JY, Hofmann SL, Frazier G, Hilgemann DW. Massive palmitoylationdependent endocytosis during reoxygenation of anoxic cardiac muscle. Elife 2: e01295, 2013
144. Linder ME, Deschenes RJ. Palmitoylation: policing protein stability and traffic. Nat Rev Mol Cell Biol 8: 74–84, 2007
145. Liu H, Abecasis GR, Heath SC, Knowles A, Demars S, Chen YJ, Roos JL, Rapoport JL, Gogos JA, Karayiorgou M. Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Proc Natl Acad Sci USA 99: 16859–16864, 2002
146. Liu J, García-Cardeña G, Sessa WC. Palmitoylation of endothelial nitric oxide synthase is necessary for optimal stimulated release of nitric oxide: implications for caveolae localization. Biochemistry 35: 13277–13281, 1996
147. Lobo S, Greentree WK, Linder ME, Deschenes RJ. Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J Biol Chem 277: 41268–41273, 2002
148. Loisel TP, Ansanay H, Adam L, Marullo S, Seifert R, Lagacé M, Bouvier M. Activation of the beta(2)-adrenergic receptor-Galpha(s) complex leads to rapid depalmitoylation and inhibition of repalmitoylation of both the receptor and Galpha(s). J Biol Chem 274: 31014–31019, 1999
149. Lu D, Sun HQ, Wang H, Barylko B, Fukata Y, Fukata M, Albanesi JP, Yin HL. Phosphatidylinositol 4-kinase IIa is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner. J Biol Chem 287: 21856–21865, 2012
150. Lynes EM, Bui M, Yap MC, Benson MD, Schneider B, Ellgaard L, Berthiaume LG, Simmen T. Palmitoylated TMX and calnexin target to the mitochondria-associated membrane. EMBO J 31: 457–470, 2012
151. Lynes EM, Raturi A, Shenkman M, Ortiz Sandoval C, Yap MC, Wu J, Janowicz A, Myhill N, Benson MD, Campbell RE, Berthiaume LG, Lederkremer GZ, Simmen T. Palmitoylation is the switch that assigns calnexin to quality control or ER Ca2+ signaling. J Cell Sci 126: 3893–3903, 2013
152. Lynes EM, Simmen T. Urban planning of the endoplasmic reticulum (ER): how diverse mechanisms segregate the many functions of the ER. Biochim Biophys Acta 1813: 1893–1905, 2011
153. Maeda A, Okano K, Park PSH, Lem J, Crouch RK, Maeda T, Palczewski K. Palmitoylation stabilizes unliganded rod opsin. Proc Natl Acad Sci USA 107: 8428–8433, 2010
154. Magee AI, Gutierrez L, McKay IA, Marshall CJ, Hall A. Dynamic fatty acylation of p21N-ras. EMBO J 6: 3353–3357, 1987
155. Marin EP, Derakhshan B, Lam TT, Davalos A, Sessa WC. Endothelial cell palmitoylproteomic identifies novel lipid-modified targets and potential substrates for protein acyl transferases. Circ Res 110: 1336–1344, 2012
156. Martin BR, Cravatt BF. Large-scale profiling of protein palmitoylation in mammalian cells. Nat Methods 6: 135–138, 2009
157. Martin BR, Wang C, Adibekian A, Tully SE, Cravatt BF. Global profiling of dynamic protein palmitoylation. Nat Methods 9: 84–89, 2012
158. McClure M, Delucas LJ, Wilson L, Ray M, Rowe SM, Wu X, Dai Q, Hong JS, Sorscher EJ, Kappes JC, Barnes S. Purification of CFTR for mass spectrometry analysis: identification of palmitoylation and other post-translational modifications. Protein Eng Des Sel 25: 7–14, 2012
159. McClure ML, Wen H, Fortenberry J, Hong JS, Sorscher EJ. S-palmitoylation regulates biogenesis of core glycosylated wild-type and F508del CFTR in a post-ER compartment. Biochem J 459: 417–425, 2014
160. McCormick PJ, Dumaresq-Doiron K, Pluviose AS, Pichette V, Tosato G, Lefrancois S. Palmitoylation controls recycling in lysosomal sorting and trafficking. Traffic 9: 1984–1997, 2008
161. Melkonian KA, Ostermeyer AG, Chen JZ, Roth MG, Brown DA. Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J Biol Chem 274: 3910–3917, 1999
162. Merrick BA, Dhungana S, Williams JG, Aloor JJ, Peddada S, Tomer KB, Fessler MB. Proteomic profiling of S-acylated macrophage proteins identifies a role for palmitoylation in mitochondrial targeting of phospholipid scramblase 3. Mol Cell Proteomics 10: M110.006007, 2011
163. Mill P, Lee AWS, Fukata Y, Tsutsumi R, Fukata M, Keighren M, Porter RM, McKie L, Smyth I, Jackson IJ. Palmitoylation regulates epidermal homeostasis and hair follicle differentiation. PLoS Genet 5: e1000748, 2009
164. Milnerwood AJ, Parsons MP, Young FB, Singaraja RR, Franciosi S, Volta M, Bergeron S, Hayden MR, Raymond LA. Memory and synaptic deficits in Hip14/DHHC17 knockout mice. Proc Natl Acad Sci USA 110: 20296–20301, 2013
165. Mitchell DA, Hamel LD, Reddy KD, Farh L, Rettew LM, Sanchez PR, Deschenes RJ. Mutations in the X-linked intellectual disability gene, zDHHC9, alter autopalmitoylation activity by distinct mechanisms. J Biol Chem 289: 18582–18592, 2014
166. Mitchell DA, Mitchell G, Ling Y, Budde C, Deschenes RJ. Mutational analysis of Saccharomyces cerevisiae Erf2 reveals a two-step reaction mechanism for protein palmitoylation by DHHC enzymes. J Biol Chem 285: 38104–38114, 2010
167. Mitchell DA, Vasudevan A, Linder ME, Deschenes RJ. Protein palmitoylation by a family of DHHC protein S-acyltransferases. J Lipid Res 47: 1118–1127, 2006
168. Mizumaru C, Saito Y, Ishikawa T, Yoshida T, Yamamoto T, Nakaya T, Suzuki T. Suppression of APP-containing vesicle trafficking and production of β-amyloid by AID/DHHC-12 protein. J Neurochem 111: 1213–1224, 2009
169. Moffett S, Adam L, Bonin H, Loisel TP, Bouvier M, Mouillac B. Palmitoylated cysteine 341 modulates phosphorylation of the beta2-adrenergic receptor by the cAMP-dependent protein kinase. J Biol Chem 271: 21490–21497, 1996
170. Moffett S, Mouillac B, Bonin H, Bouvier M. Altered phosphorylation and desensitization patterns of a human beta 2-adrenergic receptor lacking the palmitoylated Cys341. EMBO J 12: 349–356, 1993
171. Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L, Macdermott AB, Karayiorgou M, Gogos JA. Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat Neurosci 11: 1302–1310, 2008
172. Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M, Gogos JA. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet 36: 725–731, 2004
173. Munro S. Lipid rafts: elusive or illusive? Cell 115: 377–388, 2003
174. Muszbek L, Haramura G, Cluette-Brown JE, Van Cott EM, Laposata M. The pool of fatty acids covalently bound to platelet proteins by thioester linkages can be altered by exogenously supplied fatty acids. Lipids 34 Suppl: S331–S337, 1999
175. Nadolski MJ, Linder ME. Molecular recognition of the palmitoylation substrate Vac8 by its palmitoyltransferase Pfa3. J Biol Chem 284: 17720–17730, 2009
176. Navarro-Lérida I, Sánchez-Perales S, Calvo M, Rentero C, Zheng Y, Enrich C, Del Pozo MA. A palmitoylation switch mechanism regulates Rac1 function and membrane organization. EMBO J 31: 534–551, 2012
177. Niethammer P, Delling M, Sytnyk V, Dityatev A, Fukami K, Schachner M. Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis. J Cell Biol 157: 521–532, 2002
178. Nishimura A, Linder ME. Identification of a novel prenyl and palmitoyl modification at the CaaX motif of Cdc42 that regulates RhoGDI binding. Mol Cell Biol 33: 1417–1429, 2013
179. Noritake J, Fukata Y, Iwanaga T, Hosomi N, Tsutsumi R, Matsuda N, Tani H, Iwanari H, Mochizuki Y, Kodama T, Matsuura Y, Bredt DS, Hamakubo T, Fukata M. Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD- 95. J Cell Biol 186: 147–160, 2009
180. O’Brien PJ, Zatz M. Acylation of bovine rhodopsin by [3H]palmitic acid. J Biol Chem 259: 5054–5057, 1984
181. O’Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M. Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J Biol Chem 264: 7564–7569, 1989
182. Ohno Y, Kihara A, Sano T, Igarashi Y. Intracellular localization and tissue-specific distribution of human and yeast DHHC cysteine-rich domain-containing proteins. Biochim Biophys Acta 1761: 474–483, 2006
183. Olausson BES, Grossfield A, Pitman MC, Brown MF, Feller SE, Vogel A. Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes. J Am Chem Soc 134: 4324–4331, 2012
184. Ota VK, Gadelha A, Assunção IB, Santoro ML, Christofolini DM, Bellucco FT, Santos- Filho AF, Ottoni GL, Lara DR, Mari JJ, Melaragno MI, Smith MAC, Bressan RA, Belangero SI, Jackowski AP. ZDHHC8 gene may play a role in cortical volumes of patients with schizophrenia. Schizophr Res 145: 33–35, 2013
185. Ovchinnikov Yu A, Abdulaev NG, Bogachuk AS. Two adjacent cysteine residues in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitylated. FEBS Letters 230: 1–5, 1988
186. Oyama T, Miyoshi Y, Koyama K, Nakagawa H, Yamori T, Ito T, Matsuda H, Arakawa H, Nakamura Y. Isolation of a novel gene on 8p21.3–22 whose expression is reduced significantly in human colorectal cancers with liver metastasis. Genes Chromosomes Cancer 29: 9–15, 2000
187. Park S, Patterson EE, Cobb J, Audhya A, Gartenberg MR, Fox CA. Palmitoylation controls the dynamics of budding-yeast heterochromatin via the telomere-binding protein Rif1. Proc Natl Acad Sci USA 108: 14572–14577, 2011
188. Patterson GH, Hirschberg K, Polishchuk RS, Gerlich D, Phair RD, Lippincott- Schwartz J. Transport through the Golgi apparatus by rapid partitioning within a two-phase membrane system. Cell 133: 1055–1067, 2008
189. Pedram A, Razandi M, Deschenes RJ, Levin ER. DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol Biol Cell 23: 188–199, 2012
190. Pedram A, Razandi M, Lewis M, Hammes S, Levin ER. Membrane-localized estrogen receptor _ is required for normal organ development and function. Dev Cell 29: 482–490, 2014
191. Pedram A, Razandi M, Sainson RCA, Kim JK, Hughes CC, Levin ER. A conserved mechanism for steroid receptor translocation to the plasma membrane. J Biol Chem 282: 22278–22288, 2007
192. Pedro MP, Vilcaes AA, Tomatis VM, Oliveira RG, Gomez GA, Daniotti JL. 2-Bromopalmitate reduces protein deacylation by inhibition of acyl-protein thioesterase enzymatic activities. PLoS One 8: e75232, 2013
193. Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP, Bixler SA, Ambrose CM, Garber EA, Miatkowski K, Taylor FR, Wang EA, Galdes A. Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem 273: 14037–14045, 1998
194. Petrova E, Matevossian A, Resh MD. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. Oncogene 2014, doi:10.1038/onc.2013.575
195. Petrova E, Rios-Esteves J, Ouerfelli O, Glickman JF, Resh MD. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling. Nat Chem Biol 9: 247–249, 2013
196. Politis EG, Roth AF, Davis NG. Transmembrane topology of the protein palmitoyl transferase Akr1. J Biol Chem 280: 10156–10163, 2005
197. Ponimaskin E, Dityateva G, Ruonala MO, Fukata M, Fukata Y, Kobe F, Wouters FS, Delling M, Bredt DS, Schachner M, Dityatev A. Fibroblast growth factor-regulated palmitoylation of the neural cell adhesion molecule determines neuronal morphogenesis. J Neurosci 28: 8897–8907, 2008
198. Pouliot JF, Béliveau R. Palmitoylation of the glucose transporter in blood-brain barrier capillaries. Biochim Biophys Acta 1234: 191–196, 1995
199. Pralle A, Keller P, Florin EL, Simons K, Hörber JK. Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J Cell Biol 148: 997–1008, 2000
200. Prescott GR, Gorleku OA, Greaves J, Chamberlain LH. Palmitoylation of the synaptic vesicle fusion machinery. J Neurochem 110: 1135–1149, 2009
201. Qanbar R, Bouvier M. Role of palmitoylation/depalmitoylation reactions in G-proteincoupled receptor function. Pharmacol Ther 97: 1–33, 2003
202. Raymond FL, Tarpey PS, Edkins S, Tofts C, O’Meara S, Teague J, Butler A, Stevens C, Barthorpe S, Buck G, Cole J, Dicks E, Gray K, Halliday K, Hills K, Hinton J, Jones D, Menzies A, Perry J, Raine K, Shepherd R, Small A, Varian J, Widaa S, Mallya U, Moon J, Luo Y, Shaw M, Boyle J, Kerr B, Turner G, Quarrell O, Cole T, Easton DF, Wooster R, Bobrow M, Schwartz CE, Gecz J, Stratton MR, Futreal PA. Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus. Am J Hum Genet 80: 982–987, 2007
203. Ren J, Wen L, Gao X, Jin C, Xue Y, Yao X. CSSPalm 2.0: an updated software for palmitoylation sites prediction. Protein Eng Des Sel 21: 639–644, 2008
204. Ren Q, Bennett V. Palmitoylation of neurofascin at a site in the membrane-spanning domain highly conserved among the L1 family of cell adhesion molecules. J Neurochem 70: 1839–1849, 2002
205. Ren W, Jhala US, Du K. Proteomic analysis of protein palmitoylation in adipocytes. Adipocyte 2: 17–28, 2013
206. Ren W, Sun Y, Du K. DHHC17 palmitoylates ClipR-59 and modulates ClipR-59 association with the plasma membrane. Mol Cell Biol 33: 4255–4265, 2013
207. Resh MD. Use of analogs and inhibitors to study the functional significance of protein palmitoylation. Methods 40: 191–197, 2006
208. Resh MD. Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci STKE 2006: re14, 2006
209. Rocks O, Gerauer M, Vartak N, Koch S, Huang ZP, Pechlivanis M, Kuhlmann J, Brunsveld L, Chandra A, Ellinger B, Waldmann H, Bastiaens PIH. The palmitoylation machinery is a spatially organizing system for peripheral membrane proteins. Cell 141: 458–471, 2010
210. Rocks O, Peyker A, Kahms M, Verveer PJ, Koerner C, Lumbierres M, Kuhlmann J, Waldmann H, Wittinghofer A, Bastiaens PIH. An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science 307: 1746–1752, 2005
211. Roth AF, Feng Y, Chen L, Davis NG. The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J Cell Biol 159: 23–28, 2002
212. Roth AF, Wan J, Bailey AO, Sun B, Kuchar JA, Green WN, Phinney BS, Yates JR, Davis NG. Global analysis of protein palmitoylation in yeast. Cell 125: 1003–1013, 2006
213. Salaun C, Gould GW, Chamberlain LH. The SNARE proteins SNAP-25 and SNAP-23 display different affinities for lipid rafts in PC12 cells. Regulation by distinct cysteinerich domains. J Biol Chem 280: 1236–1240, 2005
214. Salaun C, Gould GW, Chamberlain LH. Lipid raft association of SNARE proteins regulates exocytosis in PC12 cells. J Biol Chem 280: 19449–19453, 2005
215. Salaun C, Greaves J, Chamberlain LH. The intracellular dynamic of protein palmitoylation. J Cell Biol 191: 1229–1238, 2010
216. Saleem AN, Chen YH, Baek HJ, Hsiao YW, Huang HW, Kao HJ, Liu KM, Shen LF, Song IW, Tu CPD, Wu JY, Kikuchi T, Justice MJ, Yen JJY, Chen YT. Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13, a gene coding for palmitoyl acyltransferase. PLoS Genet 6: e1000985, 2010
217. Sato I, Obata Y, Kasahara K, Nakayama Y, Fukumoto Y, Yamasaki T, Yokoyama KK, Saito T, Yamaguchi N. Differential trafficking of Src, Lyn, Yes and Fyn is specified by the state of palmitoylation in the SH4 domain. J Cell Sci 122: 965–975, 2009
218. Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Specific coupling ofNMDAreceptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science 284: 1845–1848, 1999
219. Schey KL, Gutierrez DB, Wang Z, Wei J, Grey AC. Novel fatty acid acylation of lens integral membrane protein aquaporin-0. Biochemistry 49: 9858–9865, 2010
220. Schmidt JW, Catterall WA. Palmitylation, sulfation, and glycosylation of the alpha subunit of the sodium channel. Role of post-translational modifications in channel assembly. J Biol Chem 262: 13713–13723, 1987
221. Schmidt MF, Schlesinger MJ. Fatty acid binding to vesicular stomatitis virus glycoprotein: a new type of post-translational modification of the viral glycoprotein. Cell 17: 813–819, 1979
222. Shahinian S, Silvius JR. Doubly-lipid-modified protein sequence motifs exhibit longlived anchorage to lipid bilayer membranes. Biochemistry 34: 3813–3822, 1995
223. Shao S, Hegde RS. Membrane protein insertion at the endoplasmic reticulum. Annu Rev Cell Dev Biol 27: 25–56, 2011
224. Shin HD, Park BL, Bae JS, Park TJ, Chun JY, Park CS, Sohn JW, Kim BJ, Kang YH, Kim JW, Kim KH, Shin TM, Woo SI. Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality. Am J Med Genet B Neuropsychiatr Genet 153B: 1167–1172, 2010
225. Shipston MJ. Ion channel regulation by protein palmitoylation. J Biol Chem 286: 8709–8716, 2011
226. Shipston MJ. Ion channel regulation by protein S-acylation. J Gen Physiol 143: 659–678, 2014
227. Shmueli A, Segal M, Sapir T, Tsutsumi R, Noritake J, Bar A, Sapoznik S, Fukata Y, Orr I, Fukata M, Reiner O. Ndel1 palmitoylation: a new mean to regulate cytoplasmic dynein activity. EMBO J 29: 107–119, 2010
228. Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF, Busch CJL, Kane C, Hübel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg ME, Draguhn A, Rehmsmeier M, Martinez J, Schratt GM. A functional screen implicates microRNA-138- dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nature 11: 705–716, 2009
229. Simons K, Ikonen E. Functional rafts in cell membranes. Nature 387: 569–572, 1997
230. Singaraja RR, Huang K, Sanders SS, Milnerwood AJ, Hines R, Lerch JP, Franciosi S, Drisdel RC, Vaid K, Young FB, Doty C, Wan J, Bissada N, Henkelman RM, Green WN, Davis NG, Raymond LA, Hayden MR. Altered palmitoylation and neuropathological deficits in mice lacking HIP14. Hum Mol Genet 20: 3899–3909, 2011
231. Singaraja RR, Kang MH, Vaid K, Sanders SS, Vilas GL, Arstikaitis P, Coutinho J, Drisdel RC, El-Husseini AED, Green WN, Berthiaume L, Hayden MR. Palmitoylation of ATPbinding cassette transporter A1 is essential for its trafficking and function. Circ Res 105: 138–147, 2009
232. Smotrys JE, Linder ME. Palmitoylation of intracellular signaling proteins: regulation and function. Annu Rev Biochem 73: 559–587, 2004
233. Song IW, Li WR, Chen LY, Shen LF, Liu KM, Yen JJY, Chen YJ, Chen YJ, Kraus VB, Wu JY, Lee MTM, Chen YT. Palmitoyl acyltransferase, Zdhhc13, facilitates bone mass acquisition by regulating postnatal epiphyseal development and endochondral ossification: a mouse model. PLoS One 9: e92194, 2014
234. Sorek N, Yalovsky S. Analysis of protein S-acylation by gas chromatography-coupled mass spectrometry using purified proteins. Nat Protoc 5: 834–840, 2010
235. Soyombo AA, Hofmann SL. Molecular cloning and expression of palmitoyl-protein thioesterase 2 (PPT2), a homolog of lysosomal palmitoyl-protein thioesterase with a distinct substrate specificity. J Biol Chem 272: 27456–27463, 1997
236. Stepanek O, Draber P, Horejsi V. Palmitoylated transmembrane adaptor proteins in leukocyte signaling. Cell Signal 26: 895–902, 2014
237. Stevens FJ, Argon Y. Protein folding in the ER. Semin Cell Dev Biol 10: 443–454, 1999
238. Stoffel RH, Inglese J, Macrae AD, Lefkowitz RJ, Premont RT. Palmitoylation increases the kinase activity of the G protein-coupled receptor kinase, GRK6. Biochemistry 37: 16053–16059, 1998
239. Sugrue RJ, Belshe RB, Hay AJ. Palmitoylation of the influenza A virus M2 protein. Virology 179: 51–56, 1990
240. Sutton LM, Sanders SS, Butland SL, Singaraja RR, Franciosi S, Southwell AL, Doty CN, Schmidt ME, Mui KKN, Kovalik V, Young FB, Zhang W, Hayden MR. Hip14l-deficient mice develop neuropathological and behavioural features of Huntington disease. Hum Mol Genet 22: 452–465, 2013
241. Swarthout JT, Lobo S, Farh L, Croke MR, Greentree WK, Deschenes RJ, Linder ME. DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J Biol Chem 280: 31141–31148, 2005
242. Takada R, Satomi Y, Kurata T, Ueno N, Norioka S, Kondoh H, Takao T, Takada S. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev Cell 11: 791–801, 2006
243. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernández-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425: 851–856, 2003
244. Thomas GM, Hayashi T, Chiu SL, Chen CM, Huganir RL. Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-R trafficking. Neuron 73: 482–496, 2012
245. Thomas GM, Hayashi T, Huganir RL, Linden DJ. DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression. J Neurosci 33: 15401–15407, 2013
246. Thomas GM, Hayashi T. Smarter neuronal signaling complexes from existing components: how regulatory modifications were acquired during animal evolution: evolution of palmitoylation-dependent regulation of AMPA-type ionotropic glutamate receptors. Bioessays 35: 929–939, 2013
247. Tian L, Jeffries O, McClafferty H, Molyvdas A, Rowe ICM, Saleem F, Chen L, Greaves J, Chamberlain LH, Knaus HG, Ruth P, Shipston MJ. Palmitoylation gates phosphorylation- dependent regulation of BK potassium channels. Proc Natl Acad Sci USA 105: 21006–21011, 2008
248. Tian L, McClafferty H, Jeffries O, Shipston MJ. Multiple palmitoyltransferases are required for palmitoylation-dependent regulation of large conductance calcium- and voltage-activated potassium channels. J Biol Chem 285: 23954–23962, 2010
249. Tian L, McClafferty H, Knaus HG, Ruth P, Shipston MJ. Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels. J Biol Chem 287: 14718–14725, 2012
250. Tom CTMB, Martin BR. Fat chance! Getting a grip on a slippery modification. ACS Chem Biol 8: 46–57, 2013
251. Tomatis VM, Trenchi A, Gomez GA, Daniotti JL. Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. PLoS One 5: e15045, 2010
252. Topinka JR, Bredt DS. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20: 125–134, 1998
253. Towler D, Glaser L. Acylation of cellular proteins with endogenously synthesized fatty acids. Biochemistry 25: 878–884, 1986
254. Towler D, Glaser L. Protein fatty acid acylation: enzymatic synthesis of an N-myristoylglycyl peptide. Proc Natl Acad Sci USA 83: 2812–2816, 1986
255. Tsutsumi R, Fukata Y, Noritake J, Iwanaga T, Perez F, Fukata M. Identification of G protein alpha subunit-palmitoylating enzyme. Mol Cell Biol 29: 435–447, 2009
256. Tulloch LB, Howie J, Wypijewski KJ, Wilson CR, Bernard WG, Shattock MJ, Fuller W. The inhibitory effect of phospholemman on the sodium pump requires its palmitoylation. J Biol Chem 286: 36020–36031, 2011
257. Valdez Taubas J, Pelham H. Swf1-dependent palmitoylation of the SNARE Tlg1 prevents its ubiquitination and degradation. EMBO J 24: 2524–2532, 2005
258. Vartak N, Papke B, Grecco HE, Rossmannek L, Waldmann H, Hedberg C, Bastiaens PIH. The autodepalmitoylating activity of APT maintains the spatial organization of palmitoylated membrane proteins. Biophys J 106: 93–105, 2014
259. Veit M, Becher A, Ahnert-Hilger G. Synaptobrevin 2 is palmitoylated in synaptic vesicles prepared from adult, but not from embryonic brain. Mol Cell Neurosci 15: 408–416, 2000
260. Veit M. Palmitoylation of virus proteins. Biol Cell 104: 493–515, 2012
261. Verkruyse LA, Hofmann SL. Lysosomal targeting of palmitoyl-protein thioesterase. J Biol Chem 271: 15831–15836, 1996
262. Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 376: 584–587, 1995
263. Vetrivel KS, Meckler X, Chen Y, Nguyen PD, Seidah NG, Vassar R, Wong PC, Fukata M, Kounnas MZ, Thinakaran G. Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts. J Biol Chem 284: 3793–3803, 2009
264. Vilas GL, Corvi MM, Plummer GJ, Seime AM, Lambkin GR, Berthiaume LG. Posttranslational myristoylation of caspase-activated p21-activated protein kinase 2 (PAK2) potentiates late apoptotic events. Proc Natl Acad Sci USA 103: 6542–6547, 2006
265. Wan J, Roth AF, Bailey AO, Davis NG. Palmitoylated proteins: purification and identification. Nat Protoc 2: 1573–1584, 2007
266. Wan J, Savas JN, Roth AF, Sanders SS, Singaraja RR, Hayden MR, Yates JR, Davis NG. Tracking brain palmitoylation change: predominance of glial change in a mouse model of Huntington’s disease. Chem Biol 20: 1421–1434, 2013
267. Wiedmer T, Zhao J, Nanjundan M, Sims PJ. Palmitoylation of phospholipid scramblase 1 controls its distribution between nucleus and plasma membrane. Biochemistry 42: 1227–1233, 2003
268. Wilson JP, Raghavan AS, Yang YY, Charron G, Hang HC. Proteomic analysis of fattyacylated proteins in mammalian cells with chemical reporters reveals S-acylation of histone H3 variants. Mol Cell Proteomics 10: M110.001198, 2011
269. Wright LP, Philips MR. Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J Lipid Res 47: 883–891, 2006
270. Xu M, St Clair D, He L. Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia: an integrated analysis of multiple datasets. Am J Med Genet B Neuropsychiatr Genet 153B: 1266–1275, 2010
271. Yamamoto Y, Chochi Y, Matsuyama H, Eguchi S, Kawauchi S, Furuya T, Oga A, Kang JJ, Naito K, Sasaki K. Gain of 5p15.33 is associated with progression of bladder cancer. Oncology 72: 132–138, 2007
272. Yan SM, Tang JJ, Huang CY, Xi SY, Huang MY, Liang JZ, Jiang YX, Li YH, Zhou ZW, Ernberg I, Wu QL, Du ZM. Reduced expression of ZDHHC2 is associated with lymph node metastasis and poor prognosis in gastric adenocarcinoma. PLoS One 8: e56366, 2013
273. Yanai A, Huang K, Kang R, Singaraja RR, Arstikaitis P, Gan L, Orban PC, Mullard A, Cowan CM, Raymond LA, Drisdel RC, Green WN, Ravikumar B, Rubinsztein DC, El-Husseini A, Hayden MR. Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function. Nat Neurosci 9: 824–831, 2006
274. Yang G, Cynader MS. Palmitoyl acyltransferase zD17 mediates neuronal responses in acute ischemic brain injury by regulating JNK activation in a signaling module. J Neurosci 31: 11980–11991, 2011
275. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132: 387–396, 2008
276. Yang W, Di Vizio D, Kirchner M, Steen H, Freeman MR. Proteome scale characterization of human S-acylated proteins in lipid raft-enriched and non-raft membranes. Mol Cell Proteomics 9: 54–70, 2010
277. Yang X, Kovalenko OV, Tang W, Claas C, Stipp CS, Hemler ME. Palmitoylation supports assembly and function of integrin-tetraspanin complexes. J Cell Biol 167: 1231–1240, 2004
278. Yap MC, Kostiuk MA, Martin DDO, Perinpanayagam MA, Hak PG, Siddam A, Majjigapu JR, Rajaiah G, Keller BO, Prescher JA, Wu P, Bertozzi CR, Falck JR, Berthiaume LG. Rapid and selective detection of fatty acylated proteins using omega-alkynyl-fatty acids and click chemistry. J Lipid Res 51: 1566–1580, 2010
279. Yeh DC, Duncan JA, Yamashita S, Michel T. Depalmitoylation of endothelial nitricoxide synthase by acyl-protein thioesterase 1 is potentiated by Ca2+-calmodulin. J Biol Chem 274: 33148–33154, 1999
280. Yeste-Velasco M, Mao X, Grose R, Kudahetti SC, Lin D, Marzec J, Vasiljević N, Chaplin T, Xue L, Xu M, Foster JM, Karnam SS, James SY, Chioni AM, Gould D, Lorincz AT, Oliver RTD, Chelala C, Thomas GM, Shipley JM, Mather SJ, Berney DM, Young BD, Lu YJ. Identification of ZDHHC14 as a novel human tumour suppressor gene. J Pathol 232: 566–577, 2014
281. Young FB, Butland SL, Sanders SS, Sutton LM, Hayden MR. Putting proteins in their place: palmitoylation in Huntington disease and other neuropsychiatric diseases. Prog Neurobiol 97: 220–238, 2012
282. Yount JS, Moltedo B, Yang YY, Charron G, Moran TM, López CB, Hang HC. Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3. Nat Chem Biol 6: 610–614, 2010
283. Yu L, Reader JC, Chen C, Zhao XF, Ha JS, Lee C, York T, Gojo I, Baer MR, Ning Y. Activation of a novel palmitoyltransferase ZDHHC14 in acute biphenotypic leukemia and subsets of acute myeloid leukemia. Leukemia 25: 367–371, 2011
284. Zeidman R, Jackson CS, Magee AI. Protein acyl thioesterases (Review). Mol Membr Biol 26: 32–41, 2009
285. Zhang MM, Wu PYJ, Kelly FD, Nurse P, Hang HC. Quantitative control of protein S-palmitoylation regulates meiotic entry in fission yeast. PLoS Biol 11: e1001597, 2013
286. Zhang YQ, Chandra SS. Oligomerization of cysteine string protein alpha mutants causing adult neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1842: 2136–2146, 2014
287. Zhao L, Lobo S, Dong X, Ault AD, Deschenes RJ. Erf4p and Erf2p form an endoplasmic reticulum-associated complex involved in the plasma membrane localization of yeast Ras proteins. J Biol Chem 277: 49352–49359, 2002
288. Zhao Y, McCabe JB, Vance J, Berthiaume LG. Palmitoylation of apolipoprotein B is required for proper intracellular sorting and transport of cholesteroyl esters and triglycerides. Mol Biol Cell 11: 721–734, 2000
289. Zheng B, DeRan M, Li X, Liao X, Fukata M, Wu X. 2-Bromopalmitate analogues as activity-based probes to explore palmitoyl acyltransferases. J Am Chem Soc 135: 7082–7085, 2013
290. Zheng H, Pearsall EA, Hurst DP, Zhang Y, Chu J, Zhou Y, Reggio PH, Loh HH, Law PY. Palmitoylation and membrane cholesterol stabilize mu-opioid receptor homodimerization and G protein coupling. BMC Cell Biol 13: 6, 2012
291. Zhou LZ, Li S, Feng QN, Zhang YL, Zhao X, Zeng YL, Wang H, Jiang L, Zhang Y. Protein S-ACYL transferase10 is critical for development and salt tolerance in Arabidopsis. Plant Cell 25: 1093–1107, 2013
292. Zhou X, Wulfsen I, Korth M, McClafferty H, Lukowski R, Shipston MJ, Ruth P, Dobrev D, Wieland T. Palmitoylation and membrane association of the stress axis regulated insert (STREX) controls BK channel regulation by protein kinase C. J Biol Chem 287: 32161–32171, 2012
293. Zou C, Ellis BM, Smith RM, Chen BB, Zhao Y, Mallampalli RK. Acyl-CoA:lysophosphatidylcholine acyltransferase I (Lpcat1) catalyzes histone protein O-palmitoylation to regulate mRNA synthesis. J Biol Chem 286: 28019–28025, 2011
294. Zuckerman DM, Hicks SW, Charron G, Hang HC, Machamer CE. Differential regulation of two palmitoylation sites in the cytoplasmic tail of the beta1-adrenergic receptor. J Biol Chem 286: 19014–19023, 2011.