Palmitoylation of the synaptic vesicle fusion machinery

Journal of Neurochemistry

Volumn 110, Issue 4, 2009, Pages 1135-1149

  Prescott, Gerald R ^a   Gorleku, Oforiwa A ^a   Greaves, Jennifer ^a   Chamberlain, Luke H ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Acylation; Cysteine string protein; Exocytosis; Palmitoylation; Soluble NSF (N ethylmaleimide sensitive factor) attachment protein receptor (SNARE)

Indexed keywords

CALCIUM ION; N ETHYLMALEIMIDE SENSITIVE FACTOR; PHOSPHOLIPID; PROTEIN PALMITOYLTRANSFERASE; SNARE PROTEIN; SYNAPTOBREVIN 2; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; SYNAPTOTAGMIN I; SYNTAXIN 1; THIOL ESTER HYDROLASE; TRANSFERASE; UNCLASSIFIED DRUG;

ACYLATION; ANIMAL CELL; CALCIUM CELL LEVEL; DROSOPHILA; EXOCYTOSIS; MEMBRANE FUSION; NEUROTRANSMITTER RELEASE; NONHUMAN; PALMITOYLATION; PRESYNAPTIC MEMBRANE; PRIORITY JOURNAL; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; REVIEW; SYNAPSE VESICLE;

ANIMALS; CALCIUM SIGNALING; HUMANS; LIPOYLATION; MEMBRANE FUSION; MEMBRANE PROTEINS; PRESYNAPTIC TERMINALS; SNARE PROTEINS; SYNAPTIC MEMBRANES; SYNAPTIC TRANSMISSION; SYNAPTIC VESICLES; SYNAPTOTAGMINS;

EID: 67651165474     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2009.06205.x     Document Type: Review

References (120)

1. Arnold C., Reisch N., Leibold C., Becker S., Prufert K., Sautter K., Palm D., Jatzke S., Buchner S. Buchner E. (2004) Structure-function analysis of the cysteine string protein in Drosophila: cysteine string, linker and C terminus. J. Exp. Biol. 207, 1323 1334.
2. Bark I. C. Wilson M. C. (1994) Human cDNA clones encoding two different isoforms of the nerve terminal protein SNAP-25. Gene 139, 291 292.
3. Binz T., Blasi J., Yamasaki S., Baumeister A., Link E., Sudhof T. C., Jahn R. Niemann H. (1994) Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. J. Biol. Chem. 269, 1617 1620.
4. Blasi J., Chapman E. R., Link E., Binz T., Yamasaki S., Camilli P. D., Sudhof T. C., Niemann H. Jahn R. (1993) Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365, 160 163.
5. Camp L. A. Hofmann S. L. (1993) Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J. Biol. Chem. 268, 22566 22574.
6. Camp L. A., Verkruyse L. A., Afendis S. J., Slaughter C. A. Hofmann S. L. (1994) Molecular cloning and expression of palmitoyl-protein thioesterase. J. Biol. Chem. 269, 23212 23219.
7. Chamberlain L. H. (2004) Detergents as tools for the purification and classification of lipid rafts. FEBS Lett. 559, 1 5.
8. Chamberlain L. H. Burgoyne R. D. (1996) Identification of a novel cysteine string protein variant and expression of cysteine string proteins in non-neuronal cells. J. Biol. Chem. 271, 7320 7323.
9. Chamberlain L. H. Burgoyne R. D. (2000) Cysteine-string protein: the chaperone at the synapse. J. Neurochem. 74, 1781 1789.
10. Chamberlain L. H. Gould G. W. (2002) The vesicle- and target-SNARE proteins that mediate Glut4 vesicle fusion are localized in detergent-insoluble lipid rafts present on distinct intracellular membranes. J. Biol. Chem. 277, 49750 49754.
11. Chapman E. R. (2008) How does synaptotagmin trigger neurotransmitter release? Annu. Rev. Biochem. 77, 615 641.
12. Chapman E. R., An S., Barton N. Jahn R. (1994) SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils. J. Biol. Chem. 269, 27427 27432.
13. Chapman E. R., Blasi J., An S., Brose N., Johnston P. A., Südhof T. C. Jahn R. (1996) Fatty acylation of synaptotagmin in PC12 cells and synaptosomes. Biochem. Biophys. Res. Comm. 225, 326 332.
14. Chen W.-Y., Shi Y.-Y., Zheng Y.-L., Zhao X.-Z., Zhang G.-J., Chen S.-Q., Yang P.-D. He L. (2004) Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8. Hum. Mol. Genet. 13, 2991 2995.
15. 2+-triggered membrane fusion. J. Cell Sci. 118, 4833 4848.
16. Couve A., Protopopov V. Gerst J. E. (1995) Yeast synaptobrevin homologs are modified posttranslationally by the addition of palmitate. Proc. Natl Acad. Sci. USA 92, 5987 5991.
17. Deck P., Pendzialek D., Biel M., Wagner M., Popkirova B., Ludolph B., Kragol G., Kuhlmann J., Giannis A. Waldmann H. (2005) Development and biological evaluation of acyl protein thioesterase 1 (APT1) inhibitors 13. Angew. Chem. Int. Edit. 44, 4975 4980. (Pubitemid 41149024)
18. Drisdel R. C. Green W. N. (2004) Labeling and quantifying sites of protein palmitoylation. BioTechniques 36, 276 285.
19. Ducker C. E., Stettler E. M., French K. J., Upson J. J. Smith C. D. (2004) Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl acyltransferase. Oncogene 23, 9230 9237.
20. Duncan J. A. Gilman A. G. (1998) A cytoplasmic acyl-protein thioesterase that removes palmitate from G-protein alpha subunits and p21RAS. J. Biol. Chem. 273, 15830 15837.
21. Duncan J. A. Gilman A. G. (2002) Characterization of Saccharomyces cerevisiae acyl-protein thioesterase 1, the enzyme responsible for G Protein alpha subunit deacylation in vivo. J. Biol. Chem. 277, 31740 31752.
22. Eggeling C., Ringemann C., Medda R. et al. (2009) Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457, 1159 1162.
23. El-Husseini A. E.-D., Schnell E., Dakoji S., Sweeney N., Zhou Q., Prange O., Gauthier-Campbell C., Aguilera-Moreno A., Nicoll R. A. Bredt D. S. (2002) Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108, 849 863.
24. Evans G. J. O., Morgan A. Burgoyne R. D. (2003) Tying everything together: the multiple roles of cysteine string protein (CSP) in regulated exocytosis. Traffic 4, 653 659.
25. Fasshauer D., Bruns D., Shen B., Jahn R. Brunger A. (1997) A structural change occurs upon binding of syntaxin to SNAP-25. J. Biol. Chem. 272, 4582 4590.
26. Fernandez-Chacon R., Wolfel M., Nishimune H. et al. (2004) The synaptic vesicle protein CSP[alpha] prevents presynaptic degeneration. Neuron 42, 237 251.
27. Fernandez-Hernando C., Fukata M., Bernatchez P. N., Fukata Y., Lin M. I., Bredt D. S. Sessa W. C. (2006) Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase. J. Cell Biol. 174, 369 377.
28. Fukata M., Fukata Y., Adesnik H., Nicoll R. A. Bredt D. S. (2004) Identification of PSD-95 palmitoylating enzymes. Neuron 44, 987 996.
29. Fukata Y., Iwanaga T. Fukata M. (2006) Systematic screening for palmitoyl transferase activity of the DHHC protein family in mammalian cells. Methods 40, 177 182.
30. Fukuda M., Kanno E., Ogata Y. Mikoshiba K. (2001) Mechanism of the SDS-resistant synaptotagmin clustering mediated by the cysteine cluster at the interface between the transmembrane and spacer domains. J. Biol. Chem. 276, 40319 40325.
31. Gonelle-Gispert C., Molinete M., Halban P. Sadoul K. (2000) Membrane localisation and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells. J. Cell Sci. 113, 3197 3205.
32. Goodwin J. S., Drake K. R., Rogers C., Wright L., Lippincott-Schwartz J., Philips M. R. Kenworthy A. K. (2005) Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway. J. Cell Biol. 170, 261 272.
33. van de Goor J. Kelly R. B. (1996) Association of Drosophila cysteine string proteins with membranes. FEBS Lett. 380, 251 256.
34. Greaves J. Chamberlain L. H. (2006) Dual role of the cysteine-string domain in membrane binding and palmitoylation-dependent sorting of the molecular chaperone cysteine-string protein. Mol. Biol. Cell 17, 4748 4759.
35. Greaves J. Chamberlain L. H. (2007) Palmitoylation-dependent protein sorting. J. Cell Biol. 176, 249 254.
36. Greaves J., Salaun C., Fukata Y., Fukata M. Chamberlain L. H. (2008) Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein. J. Biol. Chem. 283, 25014 25026.
37. Greaves J., Prescott G. R., Fukata Y., Fukata M., Salaun C. Chamberlain L. H. (2009a) 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.
38. Greaves J., Prescott G. R., Gorleku O. A. Chamberlain L. H. (2009b) The fat controller: roles of palmitoylation in intracellular protein trafficking and targeting to membrane microdomains (Review). Mol. Membr. Biol. 26, 67 79.
39. Gundersen C. B., Mastrogiacomo A., Faull K. Umbach J. A. (1994) Extensive lipidation of a Torpedo cysteine string protein. J. Biol. Chem. 269, 19197 19199.
40. Hanson P. I., Roth R., Morisaki H., Jahn R. Heuser J. E. (1997) Structure and conformational changes in NSF and its membrane receptor complexes visualized by Quick-Freeze/Deep-Etch electron microscopy. Cell 90, 523 535.
41. He Y. Linder M. E. (2009) Differential palmitoylation of the endosomal SNAREs syntaxin 7 and syntaxin 8. J. Lipid Res. 50, 398 404.
42. Heindel U., Schmidt M. F. G. Veit M. (2003) Palmitoylation sites and processing of synaptotagmin I, the putative calcium sensor for neurosecretion. FEBS Lett. 544, 57 62.
43. Hepp R., Dupont J. L., Aunis D., Langley K. Grant N. J. (2001) NGF enhances depolarization effects on SNAP-25 expression:induction of SNAP-25b isoform. Mol. Neurosci. 12, 4959 4965.
44. Huang K., Yanai A., Kang R., Arstikaitis P., Singaraja R. R., Metzler M., Mullard A., Haigh B., Gauthier-Campbell C. Gutekunst C.-A. (2004) Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Neuron 44, 977 986.
45. Huang K., Sanders S., Singaraja R., Orban P., Cijsouw T., Arstikaitis P., Yanai A., Hayden M. R. El-Husseini A. (2009) Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity. FASEB J. Epub ahead of print, doi:10.1096/fj.08-127399 T., Tsutsumi R., Noritake J., Fukata Y. Fukata M. (2009) Dynamic protein palmitoylation in cellular signaling. Prog. Lipid Res. 48, 117 127.
46. Kang R., Swayze R., Lise M. F., Gerrow K., Mullard A., Honer W. G. El-Husseini A. (2004) Presynaptic trafficking of synaptotagmin I is regulated by protein palmitoylation. J. Biol. Chem. 279, 50524 50536.
47. Kang R., Wan J., Arstikaitis P. et al. (2008) Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature 456, 904 909.
48. Karayiorgou M. Gogos J. A. (2004) The molecular genetics of the 22q11-associated schizophrenia. Mol. Brain Res. 132, 95 104.
49. Keller C. A., Yuan X., Panzanelli P., Martin M. L., Alldred M., Sassoe-Pognetto M. Luscher B. (2004) The (gamma)2 subunit of gabaa receptors is a substrate for palmitoylation by GODZ. J. Neurosci. 24, 5881 5891.
50. Kordyukova L. V., Serebryakova M. V., Baratova L. A. Veit M. (2008) 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.
51. Koticha D. K., McCarthy E. E. Baldini G. (2002) Plasma membrane targeting of SNAP-25 increases its local concentration and is necessary for SNARE complex formation and regulated exocytosis. J. Cell Sci. 115, 3341 3351.
52. Kroch A. E. Fleming K. G. (2006) Alternate interfaces may mediate homomeric and heteromeric assembly in the transmembrane domains of SNARE proteins. J. Mol. Biol. 357, 184 194.
53. Laage R., Rohde J., Brosig B. Langosch D. (2000) A conserved membrane-spanning amino acid motif drives homomeric and supports heteromeric assembly of presynaptic SNARE proteins. J. Biol. Chem. 275, 17481 17487.
54. Lane S. R. Liu Y. (1997) Characterization of the palmitoylation domain of SNAP-25. J. Neurochem. 69, 1864 1869.
55. Lang T., Bruns D., Wenzel D., Riedel D., Holroyd P., Thiele C. Jahn R. (2001) SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis. EMBO J. 20, 2202 2213.
56. Liang X., Lu Y., Neubert T. A. Resh M. D. (2002) Mass spectrometric analysis of GAP-43/neuromodulin reveals the presence of a variety of fatty acylated species. J. Biol. Chem. 277, 33032 33040.
57. Lichtenberg D., Goñi F. M. Heerklotz H. (2005) Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci. 30, 430 436.
58. Linder M. E. Deschenes R. J. (2003) New insights into the mechanisms of protein palmitoylation. Biochemistry 42, 4311 4320.
59. Lobo S., Greentree W. K., Linder M. E. Deschenes R. J. (2002) Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J. Biol. Chem. 277, 41268 41273.
60. Lu J. Y., Verkruyse L. A. Hofmann S. L. (1996) Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase. Proc. Natl Acad. Sci. USA 93, 10046 10050.
61. Magee A. I., Gutierrez L., McKay I. A., Marshall C. J. Hall A. (1987) Dynamic fatty acylation of p21N-ras. EMBO J. 6, 3353 3357.
62. Manley S., Gillette J. M., Patterson G. H., Shroff H., Hess H. F., Betzig E. Lippincott-Schwartz J. (2008) High-density mapping of single-molecule trajectories with photoactivated localization microscopy. Nat. Methods 5, 155 157.
63. Mansouri M. R., Marklund L., Gustavsson P., Davey E., Carlsson B., Larsson C., White I., Gustavson K.-H. Dahl N. (2005) Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation. Eur. J. Hum. Genet. 13, 970 977.
64. Mastrogiacomo A., Parsons S. M., Zampighi G. A., Jenden D. J., Umbach J. A. Gundersen C. B. (1994) Cysteine string proteins: a potential link between synaptic vesicles and presynaptic Ca2+ channels. Science 263, 981 982.
65. Medine C. N., Rickman C., Chamberlain L. H. Duncan R. R. (2007) Munc18-1 prevents the formation of ectopic SNARE complexes in living cells. J. Cell Sci. 120, 4407 4415.
66. Melkonian K. A., Ostermeyer A. G., Chen J. Z., Roth M. G. Brown D. A. (1999) 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.
67. Mukai J., Liu H., Burt R. A., Swor D. E., Lai W.-S., Karayiorgou M. Gogos J. A. (2004) Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat. Genet. 36, 725 731.
68. Munro S. (2003) Lipid Rafts: Elusive or Illusive? Cell 115, 377 388.
69. Nagy G., Milosevic I., Mohrmann R., Wiederhold K., Walter A. M. Sorensen J. B. (2008) The SNAP-25 linker as an adaptation toward fast exocytosis. Mol. Biol. Cell 19, 3769 3781.
70. Neher E. Sakaba T. (2008) Multiple roles of calcium ions in the regulation of neurotransmitter release. Neuron 59, 861 872.
71. Ohno Y., Kihara A., Sano T. Igarashi Y. (2006) Intracellular localization and tissue-specific distribution of human and yeast DHHC cysteine-rich domain-containing proteins. Biochim. Biophys. Acta (BBA) 1761, 474 483.
72. Ohyama T., Verstreken P., Ly C. V., Rosenmund T., Rajan A., Tien A.-C., Haueter C., Schulze K. L. Bellen H. J. (2007) Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles. J. Cell Biol. 179, 1481 1496.
73. Poirier M. A., Xiao W., Macosko J. C., Chan C., Shin Y.-K. Bennett M. K. (1998) The synaptic SNARE complex is a parallel four-stranded helical bundle. Nat. Struct. Mol. Biol. 5, 765 769.
74. Politis E. G., Roth A. F. Davis N. G. (2005) Transmembrane topology of the protein palmitoyl transferase Akr1. J. Biol. Chem. 280, 10156 10163.
75. von Poser C., Zhang J. Z., Mineo C., Ding W., Ying Y., Sudhof T. C. Anderson R. G. W. (2000) Synaptotagmin regulation of coated pit assembly. J. Biol. Chem. 275, 30916 30924.
76. Ravichandran V., Chawla A. Roche P. A. (1996) Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues. J. Biol. Chem. 271, 13300 13303.
77. Resh M. D. (2006) Trafficking and signaling by fatty-acylated and prenylated proteins. Nat. Chem. Biol. 2, 584 590.
78. Rizo J. Rosenmund C. (2008) Synaptic vesicle fusion. Nat. Struct. Mol. Biol. 15, 665 674.
79. Rocks O., Peyker A., Kahms M., Verveer P. J., Koerner C., Lumbierres M., Kuhlmann J., Waldmann H., Wittinghofer A. Bastiaens P. I. H. (2005) An acylation cycle regulates localization and activity of palmitoylated Ras isoform. Science 307, 1746 1752.
80. Roth A. F., Feng Y., Chen L. Davis N. G. (2002) The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J. Cell Biol. 159, 23 28.
81. Roth A. F., Wan J., Bailey A. O., Sun B., Kuchar J. A., Green W. N., Phinney B. S., Yates J. R. III. Davis N. G. (2006) Global analysis of protein palmitoylation in yeast. Cell 125, 1003 1013.
82. Ruiz R., Casañas J. J., Südhof T. C. Tabares L. (2008) Cysteine string protein-alpha is essential for the high calcium sensitivity of exocytosis in a vertebrate synapse. Eur. J. Neurosci. 27, 3118 3131.
83. Salaun C., James D. J. Chamberlain L. H. (2004a) Lipid rafts and the regulation of exocytosis. Traffic 5, 255 264.
84. Salaun C., James D. J., Greaves J. Chamberlain L. H. (2004b) Plasma membrane targeting of exocytic SNARE proteins. Biochim. Biophys. Acta 1693, 81 89.
85. Salaun C., Gould G. W. Chamberlain L. H. (2005a) Lipid raft association of SNARE proteins regulates exocytosis in PC12 cells. J. Biol. Chem. 280, 19449 19453.
86. Salaun C., Gould G. W. Chamberlain L. H. (2005b) The SNARE proteins SNAP-25 and SNAP-23 display different affinities for lipid rafts in PC12 cells. Regulation by distinct cysteine-rich domains. J. Biol. Chem. 280, 1236 1240.
87. Schiavo G., Rossetto O., Catsicas S., Polverino de Laureto P., DasGupta B. R., Benfenati F. Montecucco C. (1993) Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E. J. Biol. Chem. 268, 23784 23787.
88. Sieber J. J., Willig K. I., Heintzmann R., Hell S. W. Lang T. (2006) The SNARE motif is essential for the formation of syntaxin clusters in the plasma membrane. Biophys. J. 90, 2843 2851.
89. Sieber J. J., Willig K. I., Kutzner C. et al. (2007) Anatomy and dynamics of a supramolecular membrane protein cluster. Science 317, 1072 1076.
90. Sim D. S., Dilks J. R. Flaumenhaft R. (2007) Platelets possess and require an active protein palmitoylation pathway for agonist-mediated activation and in vivo thrombus formation. Arterioscler. Thromb. Vasc. Biol. 27, 1478 1485.
91. Simons K. Ikonen E. (1997) Functional rafts in cell membranes. Nature 387, 569 572.
92. Smotrys J. E. Linder M. E. (2004) Palmitoylation of intracellular signaling proteins: regulation and function. Annu. Rev. Biochem. 73, 559 587.
93. Sollner T., Bennett M. K., Whiteheart S. W., Scheller R. H. Rothman J. E. (1993a) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75, 409 418.
94. Sollner T., Whiteheart S. W., Brunner M., Erdjument-Bromage H., Geromanos S., Tempst P. Rothman J. E. (1993b) SNAP receptors implicated in vesicle targeting and fusion. Nature 362, 318 324.
95. Soyombo A. A. Hofmann S. L. (1997) 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.
96. Stowers R. S. Isacoff E. Y. (2007) Drosophila Huntingtin-interacting protein 14 is a presynaptic protein required for photoreceptor synaptic transmission and expression of the palmitoylated proteins synaptosome-associated protein 25 and cysteine string protein. J. Neurosci. 27, 12874 12883.
97. Sudhof T. C. Rothman J. E. (2009) Membrane fusion: grappling with SNARE and SM proteins. Science 323, 474 477.
98. Sutton R. B., Fasshauer D., Jahn R. Brunger A. T. (1998) Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4A resolution. Nature 395, 347 353.
99. Swarthout J. T., Lobo S., Farh L., Croke M. R., Greentree W. K., Deschenes R. J. Linder M. E. (2005) DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J. Biol. Chem. 280, 31141 31148.
100. Szule J. A. Coorssen J. R. (2003) Revisiting the role of SNAREs in exocytosis and membrane fusion. Biochim. Biophys. Acta 1641, 121 135.
101. Takamori S., Holt M., Stenius K. et al. (2006) Molecular anatomy of a trafficking organelle. Cell 127, 831 846.
102. Tong J., Borbat P. P., Freed J. H. Shin Y.-K. (2009) A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol. Proc. Natl Acad. Sci. USA 106, 5141 5146.
103. Toonen R. F. G. Verhage M. (2007) Munc18-1 in secretion: lonely Munc joins SNARE team and takes control. Trends Neurosci. 30, 564 572.
104. Umbach J. A., Zinsmaier K. E., Eberle K. K., Buchner E., Benzer S. Gundersen C. B. (1994) Presynaptic dysfunction in Drosophila csp mutants. Neuron 13, 899 907.
105. Valdez-Taubas J. Pelham H. (2005) Swf1-dependent palmitoylation of the SNARE Tlg1 prevents its ubiquitination and degradation. EMBO J. 24, 2524 2532.
106. Veit M. (2000) Palmitoylation of the 25-kDa synaptosomal protein (SNAP-25) in vitro occurs in the absence of an enzyme, but is stimulated by binding to syntaxin. Biochem. J. 345, 145 151.
107. Veit M. Schmidt M. F. G. (2001) Enzymatic depalmitoylation of viral glycoproteins with acyl-protein thioesterase 1 in vitro. Virol 288, 89 95.
108. Veit M., Söllner T. H. Rothman J. E. (1996) Multiple palmitoylation of synaptotagmin and the t-SNARE SNAP-25. FEBS Lett. 385, 119 123.
109. Veit M., Becher A. Ahnert-Hilger G. (2000) Synaptobrevin 2 is palmitoylated in synaptic vesicles prepared from adult, but not from embryonic brain. Mol. Cell. Neurosci. 15, 408 416.
110. Veit M., Laage R., Dietrich L., Wang L. Ungermann C. (2001) Vac8p release from the SNARE complex and its palmitoylation are coupled and essential for vacuole fusion. EMBO J. 20, 3145 3155.
111. Verkruyse L. A. Hofmann S. L. (1996) Lysosomal targeting of palmitoyl-protein thioesterase. J. Biol. Chem. 271, 15831 15836.
112. Vesa J., Hellsten E., Verkruyse L. A., Camp L. A., Rapola J., Santavuori P., Hofmann S. L. Peltonen L. (1995) Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 376, 584 587.
113. Wang G., Witkin J. W., Hao G., Bankaitis V. A., Scherer P. E. Baldini G. (1997) Syndet is a novel SNAP-25 related protein expressed in many tissues. J. Cell Sci. 110, 505 513.
114. Washbourne P., Cansino V., Mathews J., Graham M. E., Burgoyne R. Wilson M. (2001) Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis, but not for membrane targeting. Biochem. J. 357, 625 634.
115. Weber T., Zemelman B. V., McNew J. A., Westermann B., Gmachl M., Parlati F., Sollner T. H. Rothman J. E. (1998) SNAREpins: minimal machinery for membrane fusion. Cell 92, 759 772.
116. Williamson L. C., Halpern J. L., Montecucco C., Brown J. E. Neale E. A. (1996) Clostridial neurotoxins and substrate proteolysis in intact neurons. J. Biol. Chem. 271, 7694 7699.
117. Yanai A., Huang K., Kang R. et al. (2006) Palmitoylation of huntingtin by HIP14is essential for its trafficking and function. Nat. Neurosci. 9, 824 831.
118. 2+-calmodulin. J. Biol. Chem. 274, 33148 33154.
119. Zinsmaier K. E. Bronk P. (2001) Molecular chaperones and the regulation of neurotransmitter exocytosis. Biochem. Pharmacol. 62, 1 11.
120. Zinsmaier K. E., Eberle K. K., Buchner E., Walter N. Benzer S. (1994) Paralysis and early death in cysteine string protein mutants of Drosophila. Science 263, 977 980.