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Targeted trafficking of neurotransmitter receptors to synaptic sites

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Abstract

Emerging data are sheding light on the critical task for synapses to locally control the production of neurotransmitter receptors ultimately leading to receptor accumulation and modulation at postsynaptic sites. By analogy with the epithelial-cell paradigm, the postsynaptic compartment may be regarded as a polarized domain favoring the selective recruitment and retention of newly delivered receptors at synaptic sites. Targeted delivery of receptors to synaptic sites is facilitated by a local organization of the exocytic pathway, likely resulting from spatial cues triggered by the nerve. This review focuses on the various mechanisms responsible for regulation of receptor assembly and trafficking. A particular emphasis is given to the role of synaptic anchoring and scaffolding proteins in the sorting and routing of their receptor companion along the exocytic pathway. Other cellular components such as lipidic microdomains, the docking and fusion machinery, and the cytoskeleton also contribute to the dynamics of receptor trafficking at the synapse.

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References

  1. Lee S. H. and Sheng M. (2000) Development of neuron-neuron synapses. Curr. Opin. Neurobiol. 10, 125–131.

    Article  PubMed  CAS  Google Scholar 

  2. Duclert A. and Changeux J. P. (1995) Acetylcholine receptor gene expression at the developing neuromuscular junction. Physiol. Rev. 75, 339–368.

    PubMed  CAS  Google Scholar 

  3. Hall Z. W. and Sanes J. R. (1993) Synaptic structure and development: the neuromuscular junction. Cell 72 Suppl., 99–121.

    Article  PubMed  Google Scholar 

  4. Sanes J. R. and Lichtman J. W. (1999) Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 389–442.

    Article  PubMed  CAS  Google Scholar 

  5. Racca C., Gardiol A., and Triller A. (1997) Dendritic and postsynaptic localizations of glycine receptor alpha subunit mRNAs. J. Neurosci. 17, 1691–1700.

    PubMed  CAS  Google Scholar 

  6. Jasmin B. J., Cartaud J., Bornens M., and Changeux J. P. (1989) Golgi apparatus in chick skeletal muscle: changes in its distribution during end plate development and after denervation. Proc. Natl. Acad. Sci. USA 86, 7218–7222.

    Article  PubMed  CAS  Google Scholar 

  7. Jasmin B. J., Changeux J. P., and Cartaud J. (1990) Compartmentalization of cold-stable and acetylated microtubules in the subsynaptic domain of chick skeletal muscle fibre. Nature 344, 673–675.

    Article  PubMed  CAS  Google Scholar 

  8. Ralston E., Lu Z., and Ploug T. (1999) The organization of the Golgi complex and microtubules in skeletal muscle is fiber type-dependent. J. Neurosci. 19, 10694–705.

    PubMed  CAS  Google Scholar 

  9. Steward O. and Schuman E. M. (2001) Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24, 299–325.

    Article  PubMed  CAS  Google Scholar 

  10. Rodriguez-Boulan E. and Powell S. K. (1992) Polarity of epithelial and neuronal cells. Annu. Rev. Cell. Biol. 8, 395–427.

    Article  PubMed  CAS  Google Scholar 

  11. Nelson W. J., Yeaman C., and Grindstaff K. K. (2000) in Frontiers in Molecular Biology, Cell Polarity, (Drubin D. G., ed.), Oxford University Press, Oxford, UK, 106–140.

    Google Scholar 

  12. Matter K., Hunziker W., and Mellman I. (1992) Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants. Cell 71, 741–753.

    Article  PubMed  CAS  Google Scholar 

  13. Matter K., Yamamoto E. M., and Mellman I. (1994) Structural requirements and sequence motifs for polarized sorting and endocytosis of LDL and Fc receptors in MDCK cells. J. Cell Biol. 126, 991–1004.

    Article  PubMed  CAS  Google Scholar 

  14. Odorizzi G. and Trowbridge I. S. (1997) Structural requirements for basolateral sorting of the human transferrin receptor in the biosynthetic and endocytic pathways of Madin-Darby canine kidney cells. J. Cell Biol. 137, 1255–1264.

    Article  PubMed  CAS  Google Scholar 

  15. Simmen T., Nobile M., Bonifacino J. S., and Hunziker W. (1999) Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine motif together with an acidic amino acid cluster. Mol Cell Biol. 19, 3136–3144.

    PubMed  CAS  Google Scholar 

  16. Tugizov S., Maidji E., Xiao J., Zheng Z., and Pereira L. (1998) Human cytomegalovirus glycoprotein B contains autonomous determinants for vectorial targeting to apical membranes of polarized epithelial cells. J. Virol. 72, 7374–7386.

    PubMed  CAS  Google Scholar 

  17. Kundu A., Avalos R. T., Sanderson C. M., and Nayak D. P. (1996) Transmembrane domain of influenza virus neuraminidase, a type II protein, possesses an apical sorting signal in polarized MDCK cells. J. Virol. 70, 6508–6515.

    PubMed  CAS  Google Scholar 

  18. Chuang J. Z. and Sung C. H. (1998) The cytoplasmic tail of rhodopsin acts as a novel apical sorting signal in polarized MDCK cells. J. Cell Biol. 142, 1245–1256.

    Article  PubMed  CAS  Google Scholar 

  19. Muth T. R., Ahn J., and Caplan M. J. (1998) Identification of sorting determinants in the C-terminal cytoplasmic tails of the gamma-aminobutyric acid transporters GAT-2 and GAT-3. J. Biol. Chem. 273, 25616–25627.

    Article  PubMed  CAS  Google Scholar 

  20. Jacob R., Preuss U., Panzer P., Alfalah M., Quack S., Roth M. G., et al. (1999) Hierarchy of sorting signals in chimeras of intestinal lactasephlorizin hydrolase and the influenza virus hemagglutinin. J. Biol. Chem. 274, 8061–8067.

    Article  PubMed  CAS  Google Scholar 

  21. Scheiffele P., Peranen J., and Simons K. (1995) N-glycans as apical sorting signals in epithelial cells. Nature 378, 96–98.

    Article  PubMed  CAS  Google Scholar 

  22. Hobert M. E., Kil S. J., Medof M. E., and Carlin C. R. (1997) The cytoplasmic juxtamembrane domain of the epidermal growth factor receptor contains a novel autonomous basolateral sorting determinant. J. Biol. Chem. 272, 32901–32909.

    Article  PubMed  CAS  Google Scholar 

  23. Kozarsky K. F., Call S. M., Dower S. K., and Krieger M. (1988) Abnormal intracellular sorting of O-linked carbohydrate-deficient interleukin-2 receptors. Mol. Cell. Biol. 8, 3357–3363.

    PubMed  CAS  Google Scholar 

  24. Alfalah M., Jacob R., Preuss U., Zimmer K. P., Naim H., and Naim H. Y. (1999) O-linked glycans mediate apical sorting of human intestinal sucrase-isomaltase through association with lipid rafts. Curr. Biol. 9, 593–596.

    Article  PubMed  CAS  Google Scholar 

  25. Lisanti M. P., Caras I. W., Davitz M. A., and Rodriguez-Boulan E. (1989) Steady-state distribution and biogenesis of endogenous Madin-Darby canine kidney glycoproteins: evidence for intracellular sorting and polarized cell surface delivery. J. Cell Biol. 109, 2145–2156.

    Article  PubMed  CAS  Google Scholar 

  26. Simons K. and Ikonen E. (1997) Functional rafts in cell membranes. Nature 387, 569–572.

    Article  PubMed  CAS  Google Scholar 

  27. Puertollano R. and Alonso M. A. (1999) Targeting of MAL, a putative element of the apical sorting machinery, to glycolipid-enriched membranes requires a pre-golgi sorting event. Biochem. Biophys. Res. Commun. 254, 689–692.

    Article  PubMed  CAS  Google Scholar 

  28. Martin-Belmonte F., Puertollano R., Millan J., and Alonso M. A. (2000) The MAL protelipid is necessary for the overall apical delivery of membrane proteins in the polarized epithelial Madin-Darby canine kidney and fischer rat thyroid cell lines. Mol. Biol. Cell. 11, 2033–2045.

    PubMed  CAS  Google Scholar 

  29. Mays R. W., Beck K. A., and Nelson W. J. (1994) Organization and function of the cytoskeleton in polarized epithelial cells: a component of the protein sorting machinery. Curr. Opin. Cell Biol. 6, 16–24.

    Article  PubMed  CAS  Google Scholar 

  30. Lafont F. and Simons K. (1996) The role of microtubule-based motors in the exocytic transport of polarized cells. Semin Cell Dev. Biol. 7, 343–355.

    Article  CAS  Google Scholar 

  31. Terada S. and Hirokawa N. (2000) Moving on to the cargo problem of microtubule-dependent motors in neurons. Curr. Opin. Neurobiol. 10, 566–5673.

    Article  PubMed  CAS  Google Scholar 

  32. Söllner T., Bennett M. K., Whiteheart S. W., Scheller R. H., and Rothman J. E. (1993) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75, 409–418.

    Article  PubMed  Google Scholar 

  33. Söllner T., Whiteheart S. W., Brunner M., Erdjument-Bromage H., Geromanos S., Tempst P., and Rothman J. E. (1993) SNAP receptors implicated in vesicle targeting and fusion. Nature 362, 318–324.

    Article  PubMed  Google Scholar 

  34. Low S. H., Chapin S. J., Wimmer C., Whiteheart S. W., Komuves L. G., Mostov K. E., and Weimbs T. (1998) The SNARE machinery is involved in apical plasma membrane trafficking in MDCK cells. J. Cell Biol. 141, 1503–1513.

    Article  PubMed  CAS  Google Scholar 

  35. Galli T., Zahraoui A., Vaidyanathan V. V., Raposo G., Tian J. M., Karin M., Miemann H., and Louvard D. (1998) A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells. Mol. Biol. Cell. 9, 1437–1448.

    PubMed  CAS  Google Scholar 

  36. Dotti C. G. and Simons K. (1990) Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Post-Golgi biosynthetic trafficking. Cell 62, 63–72.

    Article  PubMed  CAS  Google Scholar 

  37. West A. E., Neve R. L., and Buckley K. M. (1997) Identification of a somatodendritic targeting signal in the cytoplasmic domain of the transferrin receptor. J. Neurosci. 17, 6038–6047.

    PubMed  CAS  Google Scholar 

  38. Keller P. and Simons K. (1997) Post-Golgi biosynthetic trafficking. J. Cell Sci. 110, 3001–3009.

    PubMed  CAS  Google Scholar 

  39. Steward O. and Levy W. B. (1982) Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J. Neurosci. 2, 284–291.

    PubMed  CAS  Google Scholar 

  40. Gardiol A., Racca C., and Triller A. (1999) Dendritic and postsynaptic protein synthetic machinery. J. Neurosci. 19, 168–179.

    PubMed  CAS  Google Scholar 

  41. Rao A. and Steward O. (1991) Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes. J. Neurosci. 11, 2881–2895.

    PubMed  CAS  Google Scholar 

  42. Torre E. R. and Steward O. (1996) Protein synthesis within dendrites: glycosylation of newly synthesized proteins in dendrites of hippocampal neurons in culture. J. Neurosci. 16, 5967–5978.

    PubMed  CAS  Google Scholar 

  43. Kiebler M. A. and DesGroseillers L. (2000) Molecular insights into mRNA transport and local translation in the mammalian nervous system. Neuron 25, 19–28.

    Article  PubMed  CAS  Google Scholar 

  44. Benson D. L. (1997) Dendritic compartmentation of NMDA receptor mRNA in cultured hippocampal neurons. Neuroreport. 8, 823–8.

    Article  PubMed  CAS  Google Scholar 

  45. Gazzaley A. H., Benson D. L., Huntley G. W., and Morrison J. H. (1997) Differential subcellular regulation of NMDAR1 protein and mRNA in dendrites of dentate gyrus granule cells after perforant path transection. J. Neurosci. 17, 2006–2017.

    PubMed  CAS  Google Scholar 

  46. Gao F. B. (1998) Messenger RNAs in dendrites: localization, stability, and implications for neuronal function. Bioessays 20, 70–78.

    Article  PubMed  CAS  Google Scholar 

  47. Martin K. C., Barad M., and Kandel E. R. (2000) Local protein synthesis and its role in synapse-specific plasticity. Curr. Opin. Neurobiol. 10, 587–92.

    Article  PubMed  CAS  Google Scholar 

  48. Gardiol A., Racca C., and Triller A. (2001) RNA transport and local protein synthesis in the dendritic compartment. Results Probl. Cell Differ. 34, 105–128.

    PubMed  CAS  Google Scholar 

  49. Mayford M., Baranes D., Podsypanina K., and Kandel E. (1996) The 3′-untranslated region of CaMKII alpha is a cis-acting signal for the localization and translation of mRNA in dendrites. Proc. Natl. Acad. Sci. USA 93, 13250–13255.

    Article  PubMed  CAS  Google Scholar 

  50. Mori Y., Imaizumi K., Katayama T., Yoneda T., and Tohyama M. (2000) Two cis-acting elements in the 3′ untranslated region of alpha-CaMKII regulate its dendritic targeting. Nat. Neurosci. 3, 1079–1084.

    Article  PubMed  CAS  Google Scholar 

  51. Blichenberg A., Rehbein M., Muller R., Garner C. C., Richter D., and Kindler S. (2001) Identification of a cis-acting dendritic targeting element in the mRNA encoding the alpha subunit of Ca2+/calmodulin-dependent protein kinase II. Eur. J. Neurosci. 13, 1881–1888.

    Article  PubMed  CAS  Google Scholar 

  52. Kislauskis E. H., Zhu X., and Singer R. H. (1994) Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype. J. Cell Biol. 127, 441–451.

    Article  PubMed  CAS  Google Scholar 

  53. Blichenberg A., Schwanke B., Rehbein M., Garner C. C., Richter D., and Kindler S. (1999) Identification of a cis-acting dendritic targeting element in MAP2 mRNAs. J. Neurosci. 19, 8818–8829.

    PubMed  CAS  Google Scholar 

  54. Gramolini A. O., Belanger G., and Jasmin B. J. (2001) Distinct regions in the 3′ untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells. J. Cell Biol. 154, 1173–1183.

    Article  PubMed  CAS  Google Scholar 

  55. Bashirullah A., Cooperstock R. L., and Lipshitz H. D. (1998) RNA localization in development. Annu. Rev. Biochem. 67, 335–394.

    Article  PubMed  CAS  Google Scholar 

  56. Kiebler M. A., Hemraj I., Verkade P., Kohrmann M., Fortes P., Marion R. M., Ortin J., and Dotti C. G. (1999) The mammalian staufen protein localizes to the somatodendritic domain of cultured hippocampal neurons: implications for its involvement in mRNA transport. J. Neurosci. 19, 288–297.

    PubMed  CAS  Google Scholar 

  57. Ross A. F., Oleynikov Y., Kislauskis E. H., Taneja K. L., and Singer R. H. (1997) Characterization of a beta-actin mRNA zipcode-binding protein. Mol. Cell. Biol. 17, 2158–2165.

    PubMed  CAS  Google Scholar 

  58. Muramatsu T., Ohmae A., and Anzai K. (1998) BC1 RNA protein particles in mouse brain contain two y-,h-element-binding proteins, translin and a 37 kDa protein. Biochem. Biophys. Res. Commun. 247, 7–11.

    Article  PubMed  CAS  Google Scholar 

  59. Severt W. L., Biber T. U., Wu X., Hecht N. B., DeLorenzo R. J., and Jakoi E. R. (1999) The suppression of testis-brain RNA binding protein and kinesin heavy chain disrupts mRNA sorting in dendrites. J. Cell Sci. 112, 3691–3702.

    PubMed  CAS  Google Scholar 

  60. Roegiers F. and Jan Y. N. (2000) Staufen: a common component of mRNA transport in oocytes and neurons? Trends Cell Biol. 10, 220–4.

    Article  PubMed  CAS  Google Scholar 

  61. Kohrmann M., Luo M., Kaether C., DesGroseillers L., Dotti C. G., and Kiebler M. A. (1999) Microtubule-dependent recruitment of Staufen-green fluorescent protein into large RNA-containing granules and subsequent dendritic transport in living hippocampal neurons. Mol. Biol. Cell. 10, 2945–2953.

    PubMed  CAS  Google Scholar 

  62. Belanger G., Lunde J. A., DesGroseillers L., and Jasmin B. J. (2000) Expression of the mRNA-binding protein Staufen at the mammalian neuromuscular junction. Mol. Biol. Cell 11, suppl., 157a.

  63. Kim-Ha J., Kerr K., and Macdonald P. M. (1995) Translational regulation of oskar mRNA by bruno, an ovarian RNA-binding protein, is essential. Cell 81, 403–412.

    Article  PubMed  CAS  Google Scholar 

  64. Norvell A., Kelley R. L., Wehr K., and Schupbach T. (1999) Specific isoforms of squid, a Drosophila hnRNP, perform distinct roles in Gurken localization during oogenesis. Genes Dev. 13, 864–876.

    PubMed  CAS  Google Scholar 

  65. Micklem D. R., Adams J., Grunert S., and St Johnston D. (2000) Distinct roles of two conserved Staufen domains in oskar mRNA localization and translation. EMBO J. 19, 1366–1377.

    Article  PubMed  CAS  Google Scholar 

  66. Wu L., Wells D., Tay J., Mendis D., Abbott M. A., Barnitt A., et al. (1998) CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. Neuron 21, 1129–1139.

    Article  PubMed  CAS  Google Scholar 

  67. Chan W. Y., Soloviev M. M., Ciruela F., and McIlhinney R. A. (2001) Molecular determinants of metabotropic glutamate receptor 1B trafficking. Mol. Cell. Neurosci. 17, 577–588.

    Article  PubMed  CAS  Google Scholar 

  68. Scott D. B., Blanpied T. A., Swanson G. T., Zhang C., and Ehlers M. D. (2001) An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing. J. Neurosci. 21, 3063–3072.

    PubMed  CAS  Google Scholar 

  69. Margeta-Mitrovic M., Jan Y. N., and Jan L. Y. (2000) A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron 27, 97–106.

    Article  PubMed  CAS  Google Scholar 

  70. Leuschner W. D. and Hoch W. (1999) Subtype-specific assembly of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits is mediated by their n-terminal domains. J. Biol. Chem. 274, 16907–16916.

    Article  PubMed  CAS  Google Scholar 

  71. Keller S. H., Lindstrom J., Ellisman M., and Taylor P. (2001) Adjacent basic amino acid residues recognized by the COPI complex and ubiquitination govern endoplasmic reticulum to cell surface trafficking of the nicotinic acetylcholine receptor alpha-Subunit. J. Biol Chem. 276, 18384–18391.

    Article  PubMed  CAS  Google Scholar 

  72. Sorenson E. M., El-Bogdadi D. G., Nong Y., and Chiappinelli V. A. (2001) α7-Containing nicotinic receptors are segregated to the somatodendritic membrane of the cholinergic neurons in the avian nucleus semilunaris. Neuroscience 103, 541–550.

    Article  PubMed  CAS  Google Scholar 

  73. Stowell J. N. and Craig A. M. (1999) Axon/dendrite targeting of metabotropic glutamate receptors by their cytoplasmic carboxy-terminal domains. Neuron 22, 525–536.

    Article  PubMed  CAS  Google Scholar 

  74. Ruberti F. and Dotti C. G. (2000) Involvement of the proximal C terminus of the AMPA receptor subunit GluR1 in dendritic sorting. J. Neurosci. 20, 1–5.

    Google Scholar 

  75. Jareb M. and Banker G. (1998) The polarized sorting of membrane proteins expressed in cultured hippocampal neurons using viral vectors. Neuron 20, 855–867.

    Article  PubMed  CAS  Google Scholar 

  76. Poyatos I., Ruberti F., Martinez-Maza R., Gimenez C., Dotti C. G., and Zafra F. (2000) Polarized distribution of glycine transporter isoforms in epithelial and neuronal cells. Mol. Cell. Neurosci. 15, 99–111.

    Article  PubMed  CAS  Google Scholar 

  77. Nadler L. S., Kumar G., and Nathanson N. M. (2001) Identification of a basolateral sorting signal for the M3 muscarinic acetylcholine receptor in Madin-Darby canine kidney cells. J. Biol. Chem. 276, 10539–10547.

    Article  PubMed  CAS  Google Scholar 

  78. McCarthy J. B., Lim S. T., Elkind N. B., Trimmer J. S., Duvoisin R. M., Rodriguez-Boulan E., and Caplan M. J. (2001) The C-terminal tail of the metabotropic glutamate receptor subtype 7 is necessary but not sufficient for cell surface delivery and polarized targeting in neurons and epithelia. J. Biol. Chem. 276, 9133–9140.

    Article  PubMed  CAS  Google Scholar 

  79. Williams B. M., Temburni M. K., Schwartz Levey M., Bertrand S., Bertrand D., and Jacob M. H. (1998) The long internal loop of the alpha 3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo. Nat. Neurosci. 1, 557–562.

    Article  PubMed  CAS  Google Scholar 

  80. Ponting C. P., Phillips C., Davies K. E., and Blake D. J. (1997) PDZ domains: targeting signalling molecules to sub-membranous sites. Bioessays 19, 469–479.

    Article  PubMed  CAS  Google Scholar 

  81. Dimitratos S. D., Woods D. F., Stathakis D. G., and Bryant P. J. (1999) Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family. Bioessays 21, 912–921.

    Article  PubMed  CAS  Google Scholar 

  82. Fanning A. S. and Anderson J. M. (1999) Protein modules as organizers of membrane structure. Curr. Opin. Cell Biol. 4, 432–439.

    Article  Google Scholar 

  83. Sheng M. and Pak D. T. (2000) Ligand-gated ion channel interactions with cytoskeletal and signaling proteins. Annu. Rev. Physiol. 62, 755–778.

    Article  PubMed  CAS  Google Scholar 

  84. Garner C. C., Nash J., and Huganir R. L. (2000) PDZ domains in synapse assembly and signalling. Trends Cell Biol. 10, 274–80.

    Article  PubMed  CAS  Google Scholar 

  85. Sheng M. and Pak D. T. (1999) Glutamate receptor anchoring proteins and the molecular organization of excitatory synapses. Ann. NY Acad. Sci. 868, 483–493.

    Article  PubMed  CAS  Google Scholar 

  86. Sheng M., and Sala C. (2001) PDZ domains and the organization of supramolecular complexes. Annu. Rev. Neurosci. 24, 1–29.

    Article  PubMed  CAS  Google Scholar 

  87. Foletti D. L., Prekeris R., and Scheller R. H. (1999) Generation and maintenance of neuronal polarity: mechanisms of transport and targeting. Neuron 23, 641–644.

    Article  PubMed  CAS  Google Scholar 

  88. Rongo C., Whitfield C. W., Rodal A., Kim S. K., and Kaplan J. M. (1998) LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia. Cell 94, 751–759.

    Article  PubMed  CAS  Google Scholar 

  89. Butz S., Okamoto M., and Sudhof T. C. (1998) A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94, 773–782.

    Article  PubMed  CAS  Google Scholar 

  90. Borg J. P., Lopez-Figueroa M. O., de Taddeo-Borg M., Kroon D. E., Turner R. S., Watson S. J., and Margolis B. (1999) Molecular analysis of the X11-mLin-2/CASK complex in brain. J. Neurosci. 19, 1307–1316.

    PubMed  CAS  Google Scholar 

  91. Whitfield C. W., Benard C., Barnes T., Hekimi S., and Kim S. K. (1999) Basolateral localization of the Caenorhabditis elegans epidermal growth factor receptor in epithelial cells by the PDZ protein LIN-10. Mol. Biol. Cell 10, 2087–2100.

    PubMed  CAS  Google Scholar 

  92. El-Husseini A. E., Craven S. E., Chetkovich D. M., Firestein B. L., Schnell E., Aoki C., and Bredt D. S. (2000) Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, post-synaptic targeting, and ion channel clustering. J. Cell Biol. 148, 159–172.

    Article  PubMed  CAS  Google Scholar 

  93. Sans N., Racca C., Petralia R. S., Wang Y. X., McCallum J., and Wenthold R. J. (2001) Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway. J. Neurosci. 21, 7506–7516.

    PubMed  CAS  Google Scholar 

  94. Chen L., Chetkovich D. M., Petralia R. S., Sweeney N. T., Kawasaki Y., Wenthold R. J., Bredt D. S., and Roger A. N. (2000) Stargazing regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408, 936–943.

    Article  PubMed  CAS  Google Scholar 

  95. Tomita S., Nicoll R. A., and Bredt D. S. (2001) PDZ protein interactions regulating glutamate receptor function and plasticity. J. Cell Biol. 153, F19-F23.

    Article  PubMed  CAS  Google Scholar 

  96. Dong H., Zhang P., Liao D., and Huganir R. L. (1999) Characterization, expression, and distribution of GRIP protein. Ann. NY Acad. Sci. 868, 535–540.

    Article  PubMed  CAS  Google Scholar 

  97. Brakeman P. R., Lanahan A. A., O’Brien R., Roche K., Barnes C. A., Hugani, R. L., and Worley P. F. (1997) Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386, 284–288.

    Article  PubMed  CAS  Google Scholar 

  98. Bloch R. J. and Froehner S. C. (1987) The relationship of the postsynaptic 43K protein to acetylcholine receptors in receptor clusters isolated from cultured rat myotubes. J. Cell Biol. 104, 645–654.

    Article  PubMed  CAS  Google Scholar 

  99. Froehner S. C., Luetje C. W., Scotland P. B., and Patrick J. (1990) The postsynaptic 43K protein clusters muscle nicotinic acetylcholine receptors in Xenopus oocytes. Neuron 5, 403–410.

    Article  PubMed  CAS  Google Scholar 

  100. Kirsch J., Wolters I., Triller A., and Betz H. (1993) Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons. Nature 366, 745–748.

    Article  PubMed  CAS  Google Scholar 

  101. Kirsch J. and Betz H. (1995) The postsynaptic localization of the glycine receptor-associated protein gephyrin is regulated by the cytoskeleton. J. Neurosci. J. Neurosci. 15, 4148–4156.

    CAS  Google Scholar 

  102. Essrich C., Lorez M., Benson J. A., Fritschy J. M. and Luscher B. (1998) Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat. Neurosci. 1, 563–571.

    Article  PubMed  CAS  Google Scholar 

  103. Ango F., Pin J. P., Tu J. C., Xiao B., Worley P. F., Bockaert J. and Fagni L. (2000) Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by homer1 proteins and neuronal excitation. J. Neurosci. 20, 8710–8716.

    PubMed  CAS  Google Scholar 

  104. Roche K. W., Tu J. C., Petralia R. S., Xiao B., Wenthold R. J. and Worley P. F. (1999) Homer 1b regulates the trafficking of group I metabotropic glutamate receptors. J. Biol. Chem. 274, 25953–25957.

    Article  PubMed  CAS  Google Scholar 

  105. Ciruela F., Soloviev M. M. and McIlhinney R. A. (1999) Co-expression of metabotropic glutamate receptor type 1alpha with homer-1a/Vesl-1S increases the cell surface expression of the receptor. Biochem. J. 341, 795–803.

    Article  PubMed  CAS  Google Scholar 

  106. Ciruela F., Soloviev M. M., Chan W. Y. and McIlhinney R. A. (2000) Homer-1c/Vesl-1L modulates the cell surface targeting of metabotropic glutamate receptor type 1alpha: evidence for an anchoring function. Mol. Cell. Neurosci. 15, 36–50.

    Article  PubMed  CAS  Google Scholar 

  107. Marchand S., Bignami F., Stetzkowski-Marden F. and Cartaud J. (2000) The myristoylated protein rapsyn is cotargeted with the nicotinic acetylcholine receptor to the postsynaptic membrane via the exocytic pathway. J. Neurosci. 20, 521–528.

    PubMed  CAS  Google Scholar 

  108. Barnes E. M. Jr. (2000) Intracellular trafficking of GABA(A) receptors. Life Sci. 66, 1063–1070.

    Article  PubMed  CAS  Google Scholar 

  109. Ikonen E. (2001) Roles of lipid rafts in membrane transport. Curr. Opin. Cell Biol. 13, 470–477.

    Article  PubMed  CAS  Google Scholar 

  110. Bruses J. L., Chauvet N. and Rutishauser U. (2001) Membrane lipid rafts are necessary for the maintenance of the (alpha)7 nicotinic acetylcholine receptor in somatic spines of ciliary neurons. J. Neurosci. 21 (2), 504–512.

    PubMed  CAS  Google Scholar 

  111. Suzuki T., Ito J., Takagi H., Saitoh F., Nawa H. and Shimizu H. (2001) Biochemical evidence for localization of AMPA-type glutamate receptor subunits in the dendritic raft. Brain Res. Mol. Brain Res. 89, 20–28.

    Article  PubMed  CAS  Google Scholar 

  112. Bruckner K., Pablo Labrador J., Scheiffele P., Herb A., Seeburg P. H. and Klein R. (1999) EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron 22 (3), 511–524.

    Article  PubMed  CAS  Google Scholar 

  113. Hirokawa N. (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519–526.

    Article  PubMed  CAS  Google Scholar 

  114. Setou M., Nakagawa T., Seog D. H. and Hirokawa N. (2000) Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288, 1796–1802.

    Article  PubMed  CAS  Google Scholar 

  115. Camus G., Jasmin B. J. and Cartaud J. (1998) Polarized sorting of nicotinic acetylcholine receptors to the postsynaptic membrane in Torpedo electrocyte. Eur. J. Neurosci. 10, 839–852.

    Article  PubMed  CAS  Google Scholar 

  116. Bignami F., Camus G., Marchand S., Bailly L., Stetzkowski-Marden F. and Cartaud J. (1998) Targeting of acetylcholine receptor and 43 kDa rapsyn to the postsynaptic membrane in Torpedo marmorata electrocyte. J. Physiol. Paris 92, 177–181.

    Article  PubMed  CAS  Google Scholar 

  117. Kirsch J., Meyer G. and Betz H. (1996) Synaptic targeting of ionotropic neurotransmitter receptors. Mol. Cell. Neurosci. 8, 93–98.

    Article  CAS  Google Scholar 

  118. Brenman J. E., Topinka J. R., Cooper E. C., McGee A. W., Rosen J., Milroy T., Ralston H. J. and Bredt D. S. (1998) Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A. J. Neurosci. 18, 8805–8813.

    PubMed  CAS  Google Scholar 

  119. Niethammer M., Valtschanoff J. G., Kapoor T. M., Allison D. W., Weinberg T. M., Craig A. M. and Sheng M. (1998) CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90. Neuron 20, 693–707.

    Article  PubMed  CAS  Google Scholar 

  120. Meyer G., Kirsch J., Betz H. and Langosh D. (1995) Identification of a gephyrin binding motif on the glycine receptor beta subunit. Neuron 15, 563–572.

    Article  PubMed  CAS  Google Scholar 

  121. Wang H. B., Bedford F. K., Brandon N. J., Moss S. J. and Olsen R. W. (1999) GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature 397, 69–72.

    Article  PubMed  CAS  Google Scholar 

  122. Hanley J. G., Koulen P., Bedford F., Gordon-Weeks P. R. and Moss S. J. (1999) The protein MAP-1B links GABA(C) receptors to the cytoskeleton at retinal synapses. Nature 397, 66–69.

    Article  PubMed  CAS  Google Scholar 

  123. Lumeng C., Phelps S., Crawford G. E., Walden P. D., Barald K. and Chamberlain J. S. (1999) Interactions between b2-syntrophin and a family of microtubule-associated serine/threonine kinases. Nat. Neurosci. 2, 611–617.

    Article  PubMed  CAS  Google Scholar 

  124. Marchand S., Stetzkowski-Marden F. and Cartaud J. (2001) Differential targeting of components of dystrophin complex to the postsynaptic membrane. Eur. J. Neurosci. 13, 221–229.

    Article  PubMed  CAS  Google Scholar 

  125. Kneussel M., Haverkamp S., Fuhrmann J. C., Wang H., Wassle H., Olsen R. W. and Betz H. (2000) The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse. Proc. Natl. Acad. Sci. USA 97, 8594–8599.

    Article  PubMed  CAS  Google Scholar 

  126. Kittler J. T., Rostaing P., Schiavo G., Fritschy J. M., Olsen R., Triller A. and Moss S. J. (2001) The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors. Mol. Cell. Neurosci. 18, 13–25.

    Article  PubMed  CAS  Google Scholar 

  127. Chilcote T. J., Galli T., Mundigl O., Edelmann L., McPherson P. S., Takei K. and De Camilli P. (1995) Cellubrevin and synaptobrevins: similar subcellular localization and biochemical properties in PC12 cells. J. Cell Biol. 129, 219–231.

    Article  PubMed  CAS  Google Scholar 

  128. Grosse G., Gross J., Tapp R., Kuchinke J., Gorsleben M., Fetter I., et al. (1999) SNAP-25 requirement for dendritic growth of hippocampal neurons. J. Neurosci Res. 56, 539–546.

    Article  PubMed  CAS  Google Scholar 

  129. Tao-Cheng J. H., Du J., and McBain C. J. (2000) Snap-25 is polarized to axons and abundant along the axolemma: an immunogold study of intact neurons. J. Neurocytol. 29, 67–77.

    Article  PubMed  CAS  Google Scholar 

  130. Song I., Kamboj S., Xia J., Dong H., Liao D., and Huganir R. L. (1998) Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21, 393–400.

    Article  PubMed  CAS  Google Scholar 

  131. Lan J. Y., Skeberdis V. A., Jover T., Grooms S. Y., Lin Y., Araneda R. C., et al. (2001) Protein kinase C modulates NMDA receptor trafficking and gating. Nat. Neurosci. 4, 382–390.

    Article  PubMed  CAS  Google Scholar 

  132. Hazuka C. D., Foletti D. L., Hsu S. C., Kee Y., Hopf F. W., and Scheller R. H. (1999) The sec6/8 complex is located at neurite outgrowth and axonal synapse-assembly domains. J. Neurosci. 19, 1324–1334.

    PubMed  CAS  Google Scholar 

  133. Strochlic L., Cartaud A., Labas V., Hoch W., Rossier J., and Cartaud J. (2001) MAGI-1c: a synaptic MAGUK interacting with MuSK at the vertebrate neuromuscular junction. J. Cell. Biol. 153, 1127–1132.

    Article  PubMed  CAS  Google Scholar 

  134. Nelson W. J. (1992) Regulation of cell surface polarity from bacteria to mammals. Science 258, 948–955.

    Article  PubMed  CAS  Google Scholar 

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  1. Biologie Cellulaire des Membranes, Institut Jacques Monod, UMR 7592, CNRS/Universités Paris 6 et Paris 7, 2 Place Jussieu, 75251, Paris Cedex 05, France

    Sophie Marchand & Jean Cartaud

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Marchand, S., Cartaud, J. Targeted trafficking of neurotransmitter receptors to synaptic sites. Mol Neurobiol 26, 117–135 (2002). https://doi.org/10.1385/MN:26:1:117

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