Protein palmitoylation: A regulator of neuronal development and function

Nature Reviews Neuroscience

Volumn 3, Issue 10, 2002, Pages 791-802

  El Husseini, Alaa El Din ^a   Bredt, David S ^b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ION CHANNEL; PALMITIC ACID DERIVATIVE; PROTEIN;

ANIMAL; BRAIN; CAPPING PHENOMENON; CYTOLOGY; GROWTH, DEVELOPMENT AND AGING; HUMAN; METABOLISM; NERVE CELL; NERVE FIBER; PHYSIOLOGY; PROTEIN MOTIF; PROTEIN TRANSPORT; REVIEW; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION;

AMINO ACID MOTIFS; ANIMALS; AXONS; BRAIN; HUMANS; ION CHANNELS; NEURONS; PALMITIC ACIDS; PROTEIN TRANSPORT; PROTEINS; RECEPTOR AGGREGATION; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION;

EID: 0036779578     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn940     Document Type: Article

References (141)

1. Casey, P J. Lipid modifications of G proteins. Curr. Opin. Cell Biol. 6, 219-225 (1994).
2. Dunphy, J. T. & Linder, M. E. Signalling functions of protein palmitoylation. Biochim. Biophys. Acta 1436, 245-261 (1998).
3. Wilcox, C., Hu, J. S. & Olson, E. N. Acylation of proteins with myristic acid occurs cotranslationally. Science 238, 1275-1278 (1987).
4. Johnson, D. R., Bhatnagar, R. S., Knoll, L. J. & Gordon, J. I. Genetics and biochemical studies of protein N-myristoylation. Annu. Rev. Biochem. 63, 869-914 (1994).
5. Zhang, F. L. & Casey, P. J. Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65, 241-269 (1996).
6. Magee, A. I. & Courtneidge, S. A. Two classes of fatty acid acylated proteins exist in eukaryotic cells. EMBO J. 4, 1137-1144 (1985).
7. McIlhinney, R. A., Pelly, S. J., Chadwick, J. K. & Cowley, G. P Studies on the attachment of myristic and palmitic acid to cell proteins in human squamous carcinoma cell lines: evidence for two pathways. EMBO J. 4, 1145-1152 (1985).
8. Hallak, H. et al. Covalent binding of arachidonate to G protein α subunits of human platelets. J. Biol. Chem. 269, 4713-4716 (1994).
9. Liang, X., Lu, Y., Neubert, T A. & Resh, M. D. Mass spectrometric analysis of GAP-43/neuromodulin reveals the presence of a variety of fatty acylated species. J. Biol. Chem. 227, 33032-33040 (2002).
10. Milligan, G., Parenti, M. & Magee, A. I. The dynamic role of palmitoylation in signal transduction. Trends Biochem. Sci. 20, 181-187 (1995).
11. Mumby, S. M. Reversible palmitoylation of signaling proteins. Curr. Opin. Cell Biol. 9, 148-154 (1997).
12. Ross, E. M. Protein modification. Palmitoylation in G-protein signaling pathways. Curr. Biol. 5, 107-109 (1995).
13. Hess, D. T., Patterson, S. I., Smith, D. S. & Skene, J. H. Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric oxide. Nature 366, 562-565 (1993).
14. Pepinsky, R. B. et al. Identification of α palmitic acid- modified form of human Sonic hedgehog. J. Biol. Chem. 273, 14037-14045 (1998).
15. Chamoun, Z. et al. Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal. Science 293, 2080-2084 (2001).
16. Hess, D. T., Slater, T. M., Wilson, M. C. & Skene, J. H. 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).
17. Washbourne, P. et al. Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis, but not for membrane targeting. Biochem. J.357, 625-634 (2001).
18. Bizzozero, O. A. The mechanism and functional roles of protein palmitoylation in the nervous system. Neuropediatrics 28, 23-26 (1997).
19. Topinka, J. R. & Bredt, D. S. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+channel, Kv1. Neuron 20, 125-134 (1998).
20. Gray, P C. et al. Primary structure and function of an A kinase anchoring protein associated with calcium channels. Neuron 20, 1017-1026 (1998).
21. DeSouza, S., Fu, J., States, B. A. & Ziff, E. B. Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters. J. Neurosci. 22, 3493-3503 (2002).
22. 3H]palmitic acid. J. Biol. Chem. 259, 5054-5057 (1984).
23. Papac, D. I., Thornburg, K. R., Bullesbach, E. E., Crouch, R. K. & Knapp, D. R. Palmitylation of a G-protein coupled receptor. Direct analysis by tandem mass spectrometry. J. Biol. Chem. 267, 16889-16894 (1992).
24. Bouvier, M. et al. Palmitoylation of G-protein-coupled receptors: a dynamic modification with functional consequences. Biochem. Soc. Trans. 23, 116-120 (1995).
25. Olson, E. N., Glaser, L. & Merlie, J. P α and β subunits of the nicotinic acetylcholine receptor contain covalently bound lipid. J. Biol. Chem. 259, 5364-5367 (1984).
26. Schmidt, J. W. & Catterall, W. A. Palmitylation, sulfation, and glycosylation of the α subunit of the sodium channel. Role of post-translational modifications in channel assembly. J. Biol. Chem. 262, 13713-13723 (1987).
27. Murray, B. A., Hoffman, S. & Cunningham, B. A. Molecular features of cell-cell adhesion molecules. Prog. Brain Res. 71, 35-45 (1987).
28. 3H]palmitic acid and mutation of cysteine-3 prevents this modification. Biochemistry 32, 8057-8061 (1993).
29. Linder, M. E. et al. Lipid modifications of G proteins: α subunits are palmitoylated. Proc. Natl Acad. Sci. USA 90, 3675-3679 (1993).
30. sα. J. Biol. Chem. 268, 25001-25008 (1993).
31. Shenoy-Scaria, A. M., Dietzen, D. J., Kwong, J., Link, D. C. & Lublin, D. M. Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. J. Cell Biol. 126, 353-363 (1994).
32. Robbins, S. M., Quintrell, N. A. & Bishop, J. M. Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae. Mol. Cell. Biol. 15, 3507-3515 (1995).
33. Hancock, J. F., Magee, A. I., Childs, J. E. & Marshall, C. J. All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57, 1167-1177 (1989).
34. Skene, J. H. & Virag, I. Posttranslational membrane attachment and dynamic fatty acylation of a neuronal growth cone protein, GAP-43. J. Cell Biol. 108, 613-624 (1989).
35. Berthiaume, L. & Resh, M. D. Biochemical characterization of a palmitoyl acyltransferase activity that palmitoylates myristoylated proteins. J. Biol. Chem. 270, 22399-22405 (1995).
36. Dunphy, J. T., Greentree, W. K., Manahan, C. L. & Linder, M. E. G-protein palmitoyltransferase activity is enriched in plasma membranes. J. Biol. Chem. 271, 7154-7159 (1996).
37. Das, A. K., Dasgupta, B., Bhattacharya, R. & Basu, J. Purification and biochemical characterization of a protein- palmitoyl acyltransferase from human erythrocytes. J. Biol. Chem. 272, 11021-11025 (1997).
38. Ueno, K. & Suzuki, Y. p260/270 expressed in embryonic abdominal leg cells of Bombyx mori can transfer palmitate to peptides. J. Biol. Chem. 272, 13519-13526 (1997).
39. Liu, L., Dudler, T. & Gelb, M. H. Purification of a protein palmitoyltransferase that acts on H-Ras protein and on a C-terminal N-Ras peptide. J. Biol. Chem. 271, 23269-23276 (1996).
40. Liu, L., Dudler, T. & Gelb, M. H. Purification of a protein palmitoyltransferase that acts on H-Ras protein and on a C-terminal N-Ras peptide. J. Biol. Chem. 274, 3252 (1999).
41. Ross, N. W. & Braun, P E. Acylation in vitro of the myelin proteolipid protein and comparison with acylation in vivo: acylation of a cysteine occurs nonenzymatically. J. Neurosci. Res. 21, 35-44 (1988).
42. O'Brien, P. J., St Jules, R. S., Reddy, T. S., Bazan, N. G. & Zatz, M. Acylation of disc membrane rhodopsin may be nonenzymatic. J. Biol. Chem. 262, 5210-5215 (1987).
43. Bano, M. C., Jackson, C. S. & Magee, A. I. Pseudo- enzymatic S-acylation of a myristoylated yes protein tyrosine kinase peptide in vitro may reflect non-enzymatic S-acylation in vivo. Biochem J. 330, 723-731 (1998).
44. Duncan, J. A. & Gilman, A. G. Autoacylation of G protein α subunits. J. Biol. Chem. 271, 23594-23600 (1996).
45. Leventis, R., Juel, G., Knudsen, J. K. & Silvius, J. R. Acyl- CoA binding proteins inhibit the nonenzymic S-acylation of cysteinyl-containing peptide sequences by long-chain acyl-CoAs. Biochemistry 36, 5546-5553 (1997).
46. Kohtz, J. D. et al. N-terminal fatty-acylation of sonic hedgehog enhances the induction of rodent ventral forebrain neurons. Development 128, 2351-2363 (2001).
47. Lee, J. D. et al. An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. Dev. Biol. 233, 122-136 (2001).
48. Jung, V., Chen, L., Hofmann, S. L., Wigler, M. & Powers, S. Mutations in the SHR5 gene of Saccharomyces cerevisiae suppress Ras function and block membrane attachment and palmitoylation of Ras proteins. Mol. Cell. Biol. 15, 1333-1342 (1995).
49. Lobo, S., Greentree, W. K., Linder, M. E. & Deschenes, R. J. Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J. Biol. Chem. 21 August 2002 (manuscript M206573200).
50. ten Brinke, A. et al. Structural requirements for palmitoylation of surfactant protein C precursor. Biochem J. 361, 663-671 (2002).
51. Mumby, S. M., Kleuss, C. & Gilman, A. G. Receptor regulation of G-protein palmitoylation. Proc. Natl Acad. Sci. USA 91, 2800-2804 (1994).
52. Liu, Y., Fisher, D. A. & Storm, D. R. Analysis of the palmitoylation and membrane targeting domain of neuromodulin (GAP-43) by site-specific mutagenesis. Biochemistry 32, 10714-10719 (1993).
53. El-Husseini, A. E. et al. Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering. J. Cell Biol. 148, 159-172 (2000).
54. Berger, M. & Schmidt, M. F. Protein fatty acyltransferase is located in the rough endoplasmic reticulum. FEBS Lett. 187, 289-294 (1985).
55. Olson, E. N. & Spizz, G. Fatty acylation of cellular proteins. Temporal and subcellular differences between palmitate and myristate acylation. J. Biol. Chem. 261, 2458-2466 (1986).
56. Dolci, E. D. & Palade, G. E. The biosynthesis and fatty acid acylation of the murine erythrocyte sialoglycoproteins. J. Biol. Chem. 260, 10728-10735 (1985).
57. El-Husseini, A. E. et al. Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108, 849-863 (2002).
58. McLaughlin, R. E. & Denny, J. B. Palmitoylation of GAP-43 by the ER-Golgi intermediate compartment and Golgi apparatus. Biochim. Biophys. Acta 1451, 82-92 (1999).
59. 2-terminal myristoylation and palmitoylation at cysteine-3. J. Cell Biol. 136, 1023-1035 (1997).
60. Peitzsch, R. M. & McLaughlin, S. Binding of acylated peptides and fatty acids to phospholipid vesicles: pertinence to myristoylated proteins. Biochemistry 32, 10436-10443 (1993).
61. Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569-572 (1997).
62. McCabe, J. B. & Berthiaume, L. G. N-terminal protein acylation confers localization to cholesterol, sphingolipid- enriched membranes but not to lipid rafts/caveolae. Mol. Biol. Cell 12, 3601-3617 (2001).
63. Lisanti, M. P. et al. Caveolae, transmembrane signalling and cellular transformation. Mol. Membr. Biol. 12, 121-124 (1995).
64. Anderson, R. G. The caveolae membrane system. Annu. Rev. Biochem. 67, 199-225 (1998).
65. Schroeder, R., London, E. & Brown, D. Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior. Proc. Natl Acad. Sci. USA 91, 12130-12134 (1994).
66. Prior, I. A. et al. GTP-dependent segregation of H-ras from lipid rafts is required for biological activity. Nature Cell Biol. 3, 368-375 (2001).
67. Rodgers, W., Crise, B. & Rose, J. K. Signals determining protein tyrosine kinase and glycosyl-phosphatidylinositol- anchored protein targeting to a glycolipid-enriched membrane fraction. Mol. Cell. Biol. 14, 5384-5391 (1994).
68. Perez, A. S. & Bredt, D. S. The N-terminal PDZ-containing region of postsynaptic density-95 mediates association with caveolar-like lipid domains. Neurosci. Lett. 258, 121-123 (1998).
69. Arni, S., Keilbaugh, S. A., Ostermeyer, A. G. & Brown, D. A. Association of GAP-43 with detergent-resistant membranes requires two palmitoylated cysteine residues. J. Biol. Chem. 273, 28478-28485 (1998).
70. Zacharias, D. A., Violin, J. D., Newton, A. C. & Tsien, R. Y. Partitioning of lipid-modified monomelic GFPs into membrane microdomains of live cells. Science 296, 913-916 (2002).
71. Wu, C., Butz, S., Ying, Y. & Anderson, R. G. Tyrosine kinase receptors concentrated in caveolae-like domains from neuronal plasma membrane. J. Biol. Chem. 272, 3554-3559 (1997).
72. Dotti, C. G. & Simons, K. Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell 62, 63-72 (1990).
73. Ledesma, M. D., Brugger, B., Bunning, C., Wieland, F. T. & Dotti, C. G. Maturation of the axonal plasma membrane requires upregulation of sphingomyelin synthesis and formation of protein-lipid complexes. EMBO J. 18, 1761-1771 (1999).
74. Dotti, C. G., Parton, R. G. & Simons, K. Polarized sorting of glypiated proteins in hippocampal neurons. Nature 349, 158-161 (1991).
75. Ledesma, M. D., Simons, K. & Dotti, C. G. Neuronal polarity: essential role of protein-lipid complexes in axonal sorting. Proc. Natl Acad. Sci. USA 95, 3966-3971 (1998).
76. El-Husseini, A. E., Craven, S. E., Brock, S. C. & Bredt, D. S. Polarized targeting of peripheral membrane proteins in neurons. J. Biol. Chem. 276, 44984-44992 (2001).
77. Strittmatter, S. M., Valenzuela, D., Kennedy, T. E., Neer, E. J. & Fishman, M. C. G0 is a major growth cone protein subject to regulation by GAP-43. Nature 344, 836-841 (1990).
78. Benowitz, L. I. & Routtenberg, A. GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. 20, 84-91 (1997).
79. Zuber, M. X., Strittmatter, S. M. & Fishman, M. C. A membrane-targeting signal in the amino terminus of the neuronal protein GAP-43. Nature 341, 345-348 (1989).
80. Sudo, Y., Valenzuela, D., Beck-Sickinger, A. G., Fishman, M. C. & Strittmatter, S. M. Palmitoylation alters protein activity: blockade of Go stimulation by GAP-43. EMBO J. 11, 2095-2102 (1992).
81. Baker, L. P. & Storm, D. R. Dynamic palmitoylation of neuromodulin (GAP-43) in cultured rat cerebellar neurons and mouse N1E-115 cells. Neurosci. Lett. 234, 156-160 (1997).
82. Patterson, S. I. & Skene, J. H. A shift in protein S-palmitoylation, with persistence of growth-associated substrates, marks a critical period for synaptic plasticity in developing brain. J. Neurobiol. 39, 423-437 (1999).
83. Niethammer, P et al. Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis. J. Cell Biol. 157, 521-532 (2002).
84. Pfanner, N. et al. Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cisternae. Cell 59, 95-102 (1989).
85. Veit, M., Sollner, T. H. & Rothman, J. E. Multiple palmitoylation of synaptotagmin and the t-SNARE SNAP-25. FEBS Lett. 385, 119-123 (1996).
86. Chamberlain, L. H. & Burgoyne, R. D. Cysteine-string protein: the chaperone at the synapse. J. Neurochem. 74, 1781-1789 (2000).
87. 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).
88. Hepler, J. R. & Gilman, A. G. G proteins. Trends Biochem. Sci. 17, 383-387 (1992).
89. Hall, R. A., Premont, R. T. & Lefkowitz, R. J. Heptahelical receptor signaling: beyond the G protein paradigm. J. Cell Biol. 145, 927-932 (1999).
90. liri, T, Backlund, P. S. Jr, Jones, T. L., Wedegaertner, P. B. & Bourne, H. R. Reciprocal regulation of Gsα by palmitate and the βγ subunit. Proc. Natl Acad. Sci. USA 93, 14592-14597 (1996).
91. Wedegaertner, P. B. & Bourne, H. R. Activation and depalmitoylation of Gsα. Cell 77, 1063-1070 (1994).
92. Jones, T. L., Degtyarev, M. Y. & Backlund, P. S. Jr. The stoichiometry of Gαs palmitoylation in its basal and activated states. Biochemistry 36, 7185-7191 (1997).
93. Tu, Y. P, Wang, J. & Ross, E. M. Inhibition of brain GzGAP and other RGS proteins by palmitoylation of G protein α subunits. Science 278, 1132-1135 (1997).
94. 2-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and β-adrenergic receptor kinase involved in its phosphorylation and desensitization. J. Neurochem. 76, 269-279 (2001).
95. 2A-adrenergic receptors confers subtype-specific agonist- promoted downregulation. Proc. Natl Acad. Sci. USA 91, 11178-11182 (1994).
96. Tu, Y., Popov, S., Slaughter, C. & Ross, E. M. Palmitoylation of a conserved cysteine in the regulator of G protein signaling (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10. J. Biol. Chem. 274, 38260-38267 (1999).
97. Stoffel, R. H., Inglese, J., Macrae, A. D., Lefkowitz, R. J. & Premont, R. T. Palmitoylation increases the kinase activity of the G protein-coupled receptor kinase, GRK6. Biochemistry 37, 16053-16059 (1998).
98. Kennedy, M. B. Signal-processing machines at the postsynaptic density. Science 290, 750-754 (2000).
99. Kornau, H.-C., Seeburg, P H. & Kennedy, M. B. Interaction of ion channels and receptors with PDZ domains. Curr. Opin. Neurobiol. 7, 368-373 (1997).
100. Garner, C. C., Nash, J. & Huganir, R. L. PDZ domains in synapse assembly and signalling. Trends Cell Biol. 10, 274-280 (2000).
101. Sheng, M. & Sala, C. PDZ domains and the organization of supramolecular complexes. Annu. Rev. Neurosci. 24, 1-29 (2001).
102. Craven, S. E. & Bredt, D. S. PDZ proteins organize synaptic signaling pathways. Cell 93, 495-498 (1998).
103. Tomita, S., Nicoll, R. A. & Bredt, D. S. PDZ protein interactions regulating glutamate receptor function and plasticity. J. Cell Biol. 153, F19-F24 (2001).
104. Cho, K. O., Hunt, C. A. & Kennedy, M. B. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9, 929-942 (1992).
105. Kistner, U. et al. SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. J. Biol. Chem. 268, 4580-4583 (1993).
106. Kim, E. et al. GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J. Cell Biol. 136, 669-678 (1997).
107. Brenman, J. E. et al. Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule- associated protein 1A. J. Neurosci. 18, 8805-8813 (1998).
108. Kim, E., Niethammer, M., Rothschild, A., Jan, Y N. & Sheng, M. Clustering of Shaker-type K+ channels by direct interaction with the PSD-95/SAP90 family of membrane- associated guanylate kinases. Nature 378, 85-88 (1995).
109. Kim, E., Cho, K.-O., Rothschild, A. & Sheng, M. Heteromultimerization and NMDA receptor clustering activity of chapsyn-110, a novel member of the PSD-95 family of synaptic proteins. Neuron 17, 103-113 (1996).
110. Tiffany, A. M. et al. PSD-95 and SAP97 exhibit distinct mechanisms for regulating K+ channel surface expression and clustering. J. Cell Biol. 148, 147-158 (2000).
111. Craven, S. E., Husseini, A. E. & Bredt, D. S. Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs. Neuron 22, 497-509 (1999).
112. Muller, B. M. et al. Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein. J. Neurosci. 15, 2354-2366 (1995).
113. Brenman, J. E., Christopherson, K. S., Craven, S. E., McGee, A. W. & Bredt, D. S. Cloning and characterization of postsynaptic density 93 (PSD-93), a nitric oxide synthase interacting protein. J. Neurosci. 16, 7407-7415 (1996).
114. Muller, B. M. et al. SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo. Neuron 17, 255-265 (1996).
115. El-Husseini, A. E. et al. Ion channel clustering by membrane- associated guanylate kinases. Differential regulation by N-terminal lipid and metal binding motifs. J. Biol. Chem. 275, 23904-23910 (2000).
116. Sans, N. et al. Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway. J. Neurosci. 21, 7506-7516 (2001).
117. Chetkovich, D. M. et al. Postsynaptic targeting of alternative postsynaptic density-95 isoforms by distinct mechanisms. J. Neurosci. 22, 6415-6425 (2002).
118. Dong, H. et al. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature 386, 279-284 (1997).
119. Srivastava, S. et al. Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP Neuron 21, 581-591 (1998).
120. Yamazaki, M. et al. Differential palmitoylation of two mouse glutamate receptor interaction protein isoforms with different N-terminal sequences. Neurosci. Lett. 304, 81-84 (2001).
121. Tsien, R. W. Calcium channels in excitable cell membranes. Annu. Rev. Physiol. 45, 341-358 (1983).
122. Hess, P. Calcium channels in vertebrate cells. Annu. Rev. Neurosci. 13, 337-356 (1990).
123. 2+ channels: role in channel function. Trends Neurosci. 21, 148-154 (1998).
124. Olcese, R. et al. The amino terminus of a calcium channel P subunit sets rates of channel inactivation independently of the subunit's effect on activation. Neuron 13, 1433-1438 (1994).
125. 2+ channel P subunit caused by palmitoylation. Proc. Natl Acad. Sci. USA 95, 4690-4695 (1998).
126. 2+ channel inactivation. Proc. Natl Acad. Sci. USA 97, 9293-9298 (2000).
127. 2+ channels due to phosphorylation by cAMP-dependent protein kinase. Nature 364, 240-243 (1993).
128. Takimoto, K., Yang, E. K. & Conforti, L. Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels. J. Biol. Chem. 277, 26904-26911 (2002).
129. Malinow, R., Mainen, Z. F. & Hayashi, Y. LTP mechanisms: from silence to four-lane traffic. Curr. Opin. Neurobiol. 10, 352-357 (2000).
130. Malenka, R. C. & Nicoll, R. A. Long-term potentiation — a decade of progress? Science 285, 1870-1874 (1999).
131. El-Husseini, A. E., Schnell, E., Chetkovich, D. M., Nicoll, R. A. & Bredt, D. S. PSD-95 involvement in maturation of excitatory synapses. Science 290, 1364-1368 (2000).
132. Kornau, H.-C., Schenker, L. T., Kennedy, M. B. & Seeburg, P H. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269, 1737-1740 (1995).
133. 2+-channel y subunit. Nature Genet. 19, 340-347 (1998).
134. Hashimoto, K. et al. Impairment of AMPA receptor function in cerebellar granule cells of ataxic mutant mouse stargazer. J. Neurosci. 19, 6027-6036 (1999).
135. Chen, L. et al. Stargazin mediates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408, 936-943 (2000).
136. Webb, Y., Hermida-Matsumoto, L. & Resh, M. D. Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids. J. Biol. Chem. 275, 261-270 (2000).
137. Migaud, M. et al. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396, 433-439 (1998).
138. RAS. J. Biol. Chem. 273, 15830-15837 (1998).
139. 2+-calmodulin. J. Biol. Chem. 274, 33148-33154 (1999).
140. Camp, L. A., Verkruyse, L. A., Afendis, S. J., Slaughter, C. A. & Hofmann, S. L. Molecular cloning and expression of palmitoyl-protein thioesterase. J. Biol. Chem. 269, 23212-23219 (1994).
141. Vesa, J. et al. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 376, 584-587 (1995).