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Genetic and molecular analysis of synaptic vesicle recycling in Drosophila

  • Published:
Journal of Neurocytology

Abstract

Following exocytosis, one of the major presynaptic events is replenishing synaptic vesicles (SVs) to ensure the possibility of continuous synaptic transmission. The nerve terminal is thought to recycle SVs through clathrin-mediated endocytosis and by a clathrin-independent pathway called ‘kiss and run’. This review highlights the use of the genetic model organism, the fruit fly (Drosophila melanogaster), in dissecting the molecular mechanisms of clathrin-mediated endocytosis in recycling SVs at neuromuscular junctions (NMJs). Analyses of endocytotic mutants in Drosophila indicate that clathrin-mediated endocytosis may be essential for SV recycling, including a putative fast recycling mechanism uncovered recently. Further, a rather complex picture begins to emerge suggesting that clathrin-mediated endocytosis involves several sequential steps mediated by a large number of proteins. Finally, these studies also reveal that SV proteins may be selectively retrieved into nascent SVs by clathrin accessory proteins and defects in protein retrieval have significant impacts on synaptic transmission. Following the completion of the Drosophila Genome Project and the development of gene targeting and RNAi approaches, genetic studies in Drosophila have become increasingly efficient. Hence, Drosophila is expected to continue to serve as an important model organism for studies of SV recycling.

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References

  • ADAMS, M. D., CELNIKER, S. E., HOLT, R. A., EVANS, C. A., GOCAYNE, J. D. et al. (2000) The genome sequence of Drosophila melanogaster. Science 287, 218–2195.

    PubMed  Google Scholar 

  • AHLE, S. & UNGEWICKELL, E. (1986) Purification and properties of a new clathrin assembly protein. EMBO J. 5, 314–3149.

    PubMed  Google Scholar 

  • AHLE, S. & UNGEWICKELL, E. (1990) Auxilin, a newly identified clathrin-associated protein in coated vesicles from bovine brain. J. Cell Biol. 111, 1–29.

    PubMed  Google Scholar 

  • ANDREWS, J., SMITH, M., MERAKOVSKY, J., COULSON, M., HANNAN, F. & KELLY, L. E. (1996) The stoned locus of Drosophila melanogaster produces a dicistronic transcript and encodes two distinct polypeptides. Genetics 143, 169–1711.

    PubMed  Google Scholar 

  • ARTALEJO, C. R., ELHAMDANI, A. & PALFREY, H. C. (2002) Sustained stimulation shifts the mechanism of endocytosis from dynamin-1-dependent rapid endocytosis to clathrin-and dynamin-2-mediated slow endocytosis in chromaffin cells. Proc. Natl. Acad. Sci. USA 99, 635–6363.

    PubMed  Google Scholar 

  • ARTALEJO, C. R., HENLEY, J. R., MCNIVEN, M. A. & PALFREY, H. C. (1995) Rapid endocytosis coupled to exocytosis in adrenal chromaffin cells involves Ca2+, GTP, and dynamin but not clathrin. Proc. Natl. Acad. Sci. USA 92, 832–8332.

    PubMed  Google Scholar 

  • ATWOOD, H. L., GOVIND, C. K. & WU, C. F. (1993) Differential ultrastructure of synaptic terminals on ventral longitudinal abdominal muscles in Drosophila larvae. J. Neurobiol. 24, 100–1024.

    PubMed  Google Scholar 

  • AUGUSTINE, G. J., BURNS, M. E., DEBELLO, W. M., HILFIKER, S., MORGAN, J. R., SCHWEIZER, F. E., TOKUMARU, H. & UMAYAHARA, K. (1999) Proteins involved in synaptic vesicle trafficking. J. Physiol. 520, 3–41.

    PubMed  Google Scholar 

  • BAZINET, C., KATZEN, A. L., MORGAN, M., MAHOWALD, A. P. & LEMMON, S. K. (1993) The Drosophila clathrin heavy chain gene: Clathrin function is essential in a multicellular organism. Genetics 134, 111–1134.

    PubMed  Google Scholar 

  • BENMERAH, A., BAYROU, M., CERF-BENSUSSAN, N. & DAUTRY-VARSAT, A. (1999) Inhibition of clathrincoated pit assembly by an Eps15 mutant. J. Cell Sci. 112, 130–1311.

    PubMed  Google Scholar 

  • BRAELL, W. A., SCHLOSSMAN, D. M., SCHMID, S. L. & ROTHMAN, J. E. (1984) Dissociation of clathrin coats coupled to the hydrolysis of ATP: Role of an uncoating ATPase. J. Cell Biol. 99, 73–741.

    PubMed  Google Scholar 

  • BRAND, A. H. & PERRIMON, N. (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 40–415.

    PubMed  Google Scholar 

  • BETZ, W. J. & BEWICK, G. S. (1992) Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255, 20–203.

    PubMed  Google Scholar 

  • BROADIE, K., BELLEN, H. J., DIANTONIO, A., LITTLETON, J. T. & SCHWARZ, T. L. (1994) Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission. Proc. Natl. Acad. Sci. USA 91, 1072–10731.

    PubMed  Google Scholar 

  • BRODIN, L., LOW, P. & SHUPLIAKOV, O. (2001) Sequential steps in clathrin-mediated synaptic vesicle endocytosis. Curr. Opin. Neurobiol. 10, 31–320.

    Google Scholar 

  • BRODSKY, F. M., CHEN, C. Y., KNUEHL, C., TOWLER, M. C. & WAKEHAM, D. E. (2001) Biological basket weaving: Formation and function of clathrin-coated vesicles. Annu. Rev. Cell Dev. Biol. 17, 51–568.

    PubMed  Google Scholar 

  • BRONK, P., WENNIGER, J. J., DAWSON-SCULLY, K., GUO, X., HONG, S., ATWOOD, H. L. & ZINSMAIER, K. E. (2001) Drosophila Hsc70-4 is critical for neurotransmitter exocytosis in vivo. Neuron 30, 47–488.

    PubMed  Google Scholar 

  • BUDNIK, V. & GRAMATES, L. S. (1999) Neuromuscular Junctions in Drosophila. International Review of Neurobiology vol. 43 (edited byBRADLEY, R. J., HARRIS, R. A. & JENNER, P.) San Diego, CA, USA, Academic Press.

    Google Scholar 

  • BUTLER, M. H., DAVID, C., OCHOA, G. C., FREYBERG, Z., DANIELL, L., GRABS, D., CREMONA, O. & DE CAMILLI, P. (1997) Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle. J. Cell Biol. 137, 135–1367.

    PubMed  Google Scholar 

  • CADAVID, A. L., GINZEL, A. & FISCHER, J. A. (2000) The function of the Drosophila fat facets deubiquitinating enzyme in limiting photoreceptor cell number is intimately associated with endocytosis. Development 127, 172–1736.

    PubMed  Google Scholar 

  • CECCARELLI, B., GROHOVAZ, F. & HURLBUT, W. P. (1979a) Freeze-fracture studies of frog neuromuscular junctions during intense release of neurotransmitter. I. Effects of black widow spider venom and Ca2+-free solutions on the structure of the active zone. J. Cell Biol. 81, 16–177.

    PubMed  Google Scholar 

  • CECCARELLI, B., GROHOVAZ, F. & HURLBUT, W. P. (1979b) Freeze-fracture studies of frog neuromuscular junctions during intense release of neurotransmitter. II. Effects of electrical stimulation and high potassium. J. Cell Biol. 81, 17–192.

    PubMed  Google Scholar 

  • CECCARELLI, B., HURLBUT, W. P. & MAURO, A. (1973) Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. J. Cell Biol. 57, 49–524.

    PubMed  Google Scholar 

  • CECCARELLI, B., HURLBUT, W. P. & MAURO, A. (1972) Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation. J. Cell Biol. 54, 3–38.

    PubMed  Google Scholar 

  • CHANG, H. C., NEWMYER, S. L., HULL, M. J., EBERSOLD, M., SCHMID, S. L. & MELLMAN, I. (2002) Hsc70 is required for endocytosis and clathrin function in Drosophila. J. Cell Biol. 159, 47–487.

    PubMed  Google Scholar 

  • CHEN, H., FRE, S., SLEPNEV, V. I., CAPUA, M. R., TAKEI, K., BUTLER, M. H., DI FIORE, P. P. & DE CAMILLI, P. (1998) Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature 394, 79–797.

    PubMed  Google Scholar 

  • CHEN, M. S., OBAR, R. A., SCHROEDER, C. C., AUSTIN, T. W., POODRY, C. A., WADSWORTH, S. C. & VALLEE, R. B. (1991) Multiple forms of dynamin are encoded by shibire, a Drosophila gene involved in endocytosis. Nature 351, 58–586.

    PubMed  Google Scholar 

  • CHEN, X., ZHANG, B. & FISCHER, J. A. (2002) A specific protein substrate for a deubiquitinating enzyme: Liquid facets is the substrate of Fat facets. Genes Dev. 16, 28–294.

    PubMed  Google Scholar 

  • CLARK, S. G., SHURLAND, D. L., MEYEROWITZ, E. M., BARGMANN, C. I. & VAN DER BLIEK, A. M. (1997) A dynamin GTPase mutation causes a rapid and reversible temperature-inducible locomotion defect in C. elegans. Proc. Natl. Acad. Sci. USA 94, 1043–10443.

    PubMed  Google Scholar 

  • COCHILLA, A. J., ANGLESON, J. K. & BETZ, W. J. (1999) Monitoring secretory membrane with FM1-43 fluorescence. Annu. Rev. Neurosci. 22, –10.

    PubMed  Google Scholar 

  • CONFALONIERI, S. & DI FIORE, P. P. (2002) The Eps15 homology (EH) domain. FEBS Lett. 513, 2–29.

    PubMed  Google Scholar 

  • CREMONA, O., DI PAOLO, G., WENK, M. R., LUTHI, A., KIM, W. T., TAKEI, K., DANIELL, L., NEMOTO, Y., SHEARS, S. B., FLAVELL, R. A., MCCORMICK, D. A. & DE CAMILLI, P. (1999) Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell 99, 17–188.

    PubMed  Google Scholar 

  • CROWTHER, R. A. & PEARSE, B. M. (1981) Assembly and packing of clathrin into coats. J. Cell Biol. 91, 79–797.

    PubMed  Google Scholar 

  • DAVID, C., MCPHERSON, P. S., MUNDIGL, O. & DE CAMILLI, P. (1996) A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc. Natl. Acad. Sci. USA 93, 33–335.

    PubMed  Google Scholar 

  • DE CAMILLI, P. & TAKEI, K. (1996) Molecular mechanisms in synaptic vesicle endocytosis and recycling. Neuron 16, 48–486.

    PubMed  Google Scholar 

  • DE CAMILLI, P., CHEN, H., HYMAN, J., PANEPUCCI, E., BATEMAN, A. & BRUNGER, A. T. (2002) The ENTH domain. FEBS Lett. 513, 1–18.

    PubMed  Google Scholar 

  • DELGADO, R., MAUREIRA, C., OLIVA, C., KIDOKORO, Y. & LABARCA, P. (2000) Size of vesicle pools, rates of mobilization, and recycling at neuromuscular synapses of a Drosophila mutant, shibire. Neuron 28, 94–953.

    PubMed  Google Scholar 

  • DELL'ANGELICA, E. C., MULLINS, C. & BONIFACINO, J. S. (1999) AP-4, a novel protein complex related to clathrin adaptors. J. Biol Chem. 274, 727–7285.

    PubMed  Google Scholar 

  • DIANTONIO, A. & SCHWARZ, T. L. (1994) The effect on synaptic physiology of synaptotagmin mutations in Drosophila. Neuron 12, 90–920.

    PubMed  Google Scholar 

  • DIANTONIO, A., HAGHIGHI, A. P., PORTMAN, S. L., LEE, J. D., AMARANTO, A. M. & GOODMAN, C. S. (2001) Ubiquitination-dependent mechanisms regulate synaptic growth and function. Nature 412, 44–452.

    PubMed  Google Scholar 

  • DIANTONIO, A., PARFITT, K. D. & SCHWARZ, T. L. (1993) Synaptic transmission persists in synaptotagmin mutants of Drosophila. Cell 73, 128–1290.

    PubMed  Google Scholar 

  • DI PAOLO, G., SANKARANARAYANAN, S., WENK, M. R., DANIELL, L., PERUCCO, E., CALDARONE, B. J., FLAVELL, R., PICCIOTTO, M. R., RYAN, T. A., CREMONA, O. & DE CAMILLI, P. (2002) Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33, 78–804.

    PubMed  Google Scholar 

  • DREYLING, M. H., MARTINEZ-CLIMENT, J. A., ZHENG, M., MAO, J., ROWLEY, J. D. & BOHLANDER, S. K. (1996) The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family. Proc. Natl. Acad. Sci. USA 93, 480–4809.

    PubMed  Google Scholar 

  • DUBNAU, J., GRADY, L., KITAMOTO, T. & TULLY, T. (2001) Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory. Nature 411, 47–480.

    PubMed  Google Scholar 

  • ENGQVIST-GOLDSTEIN, A. E., KESSELS, M. M., CHOPRA, V. S., HAYDEN, M. R. & DRUBIN, D. G. (1999) An actin-binding protein of the Sla2/Huntingtin interacting protein 1 family is a novel component of clathrin-coated pits and vesicles. J. Cell Biol. 147, 150–1518.

    PubMed  Google Scholar 

  • ESTES, P. S., ROOS, J., VAN DER BLIEK, A., KELLY, R. B., KRISHNAN, K. S. & RAMASWAMI, M. (1996) Traffic of dynamin within individual Drosophila synaptic boutons relative to compartment-specific markers. J. Neurosci. 16, 544–5456.

    PubMed  Google Scholar 

  • ESTES, P. S., JACKSON, T. C. STIMSON, D. T., SANYAL, S. KELLY, L. E. & RAMASWAMI, M. (2003) Functional dissection of a eukaryotic dicistronic gene: Transgenic Stonedb, but not Stoneda, restores normal synaptic properties to Drosophila stoned mutants. Genetics 165, 18–196.

    PubMed  Google Scholar 

  • FARSAD, K., RINGSTAD, N., TAKEI, K., FLOYD, S. R., ROSE, K. & DE CAMILLI, P. (2001) Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J. Cell Biol. 155, 19–200.

    PubMed  Google Scholar 

  • FAZIOLI, F., MINICHIELLO, L., MATOSKOVA, B., WONG, W. T. & DI FIORE, P. P. (1993) eps15, a novel tyrosine kinase substrate, exhibits transforming activity. Mol. Cell Biol. 13, 581–5828.

    PubMed  Google Scholar 

  • FERGESTAD, T. & BROADIE, K. (2001) Interaction of stoned and synaptotagmin in synaptic vesicle endocytosis. J. Neurosci. 21, 121–1227.

    PubMed  Google Scholar 

  • FERGESTAD, T., DAVIS, W. S. & BROADIE, K. (1999) The stoned proteins regulate synaptic vesicle recycling in the presynaptic terminal. J. Neurosci. 19, 584–5860.

    PubMed  Google Scholar 

  • FESCE, R., GROHOVAZ, R., VALTORTA, F. & MELDOLESI, J. (1994) Neurotransmitter release: Fusion or 'kiss-and-run'. Trend in Cell Biol. 4, –4.

    Google Scholar 

  • FIRE, A., XU, S., MONTGOMERY, M. K., KOSTAS, S. A., DRIVER, S. E. & MELLO, C. C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 80–811.

    PubMed  Google Scholar 

  • FISCHER-VIZE, J. A., RUBIN, G. M. & LEHMANN, R. (1992) The fat facets gene is required for Drosophila eye and embryo development. Development 116, 98–1000.

    PubMed  Google Scholar 

  • FORD, M. G., PEARSE, B. M., HIGGINS, M. K., VALLIS, Y., OWEN, D. J., GIBSON, A., HOPKINS, C. R., EVANS, P. R. & MCMAHON, H. T. (2001) Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science 291, 105–1055.

    PubMed  Google Scholar 

  • FORD, M. G., MILLS, I. G., PETER, B. J., VALLIS, Y., PRAEFCKE, G. J., EVANS, P. R. & MCMAHON, H. T. (2002) Curvature of clathrin-coated pits driven by epsin. Nature 419, 36–366.

    PubMed  Google Scholar 

  • FUKUDA, M., MOREIRA, J. E., LEWIS, F. M., SUGIMORI, M., NIINOBE, M., MIKOSHIBA, K. & LLINAS, R. (1995) Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antibody injection into the squid giant synapse preterminal. Proc. Natl. Acad. Sci. USA 92, 1070–10712.

    PubMed  Google Scholar 

  • GAD, H., RINGSTAD, N., LOW, P., KJAERULFF, O., GUSTAFSSON, J., WENK, M., DI PAOLO, G., NEMOTO, Y., CRUN, J., ELLISMAN, M. H., DE CAMILLI, P., SHUPLIAKOV, O. & BRODIN, L. (2000) Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin. Neuron 27, 30–312.

    PubMed  Google Scholar 

  • GALL, W. E., HIGGINBOTHAM, M. A., CHEN, C., INGRAM, M. F., CYR, D. M. & GRAHAM, T. R. (2000) The auxilin-like phosphoprotein Swa2p is required for clathrin function in yeast. Curr. Biol. 10, 134–1358.

    PubMed  Google Scholar 

  • GAO, B. C., BIOSCA, J., CRAIG, E. A., GREENE, L. E. & EISENBERG, E. (1991) Uncoating of coated vesicles by yeast hsp70 proteins. J. Biol. Chem. 266, 1956–19571.

    PubMed  Google Scholar 

  • GONZALEZ-GAITAN, M. & JACKLE, H. (1997) Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell 88, 76–776.

    PubMed  Google Scholar 

  • GRABS, D., SLEPNEV, V. I., SONGYANG, Z., DAVID, C., LYNCH, M., CANTLEY, L. C. & DE CAMILLI, P. (1997) The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. J. Biol. Chem. 272, 1341–13425.

    PubMed  Google Scholar 

  • GRANT, D., UNADKAT, S., KATZEN, A., KRISHNAN, K. S. & RAMASWAMI, M. (1998) Probable mechanisms underlying interallelic complementation and temperature-sensitivity of mutations at the shibire locus of Drosophila melanogaster. Genetics 149, 101–1030.

    PubMed  Google Scholar 

  • GRIGLIATTI, T. A., HALL, L., ROSENBLUTH, R. & SUZUKI, D. T. (1973) Temperature-sensitive mutations in Drosophila melanogaster. XIV.Aselection of immobile adults. Mol. Gen. Genet. 120, 10–114.

    PubMed  Google Scholar 

  • GUICHET, A., WUCHERPFENNIG, T., DUDU, V., ETTER, S., WILSCH-BRAUNIGER, M., HELLWIG, A., GONZALEZ-GAITAN, M., HUTTNER, W. B. & SCHMIDT, A. A. (2002) Essential role of endophilin A in synaptic vesicle budding at theDrosophila neuromuscular junction. EMBO J. 21, 166–1672.

    PubMed  Google Scholar 

  • HARRIS, T. W., HARTWIEG, E., HORVITZ, H. R. & JORGENSEN, E. M. (2000) Mutations in synaptojanin disrupt synaptic vesicle recycling. J. Cell Biol. 150, 58–600.

    PubMed  Google Scholar 

  • HARRIS, T. W., SCHUSKE, K. & JORGENSEN, E. M. (2001) Studies of synaptic vesicle endocytosis in the nematode C. elegans. Traffic 2, 59–605.

    PubMed  Google Scholar 

  • HEUSER, J. E. & REESE, T. S. (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J. Cell Biol. 57, 31–344.

    PubMed  Google Scholar 

  • HEUSER, J. E. & REESE, T. S. (1981) Structural changes after transmitter release at the frog neuromuscular junction. J. Cell Biol. 88, 56–580.

    PubMed  Google Scholar 

  • HEUSER, J. (1980) Three-dimensional visualization of coated vesicle formation in fibroblasts. J. Cell Biol. 84, 56–583.

    PubMed  Google Scholar 

  • HOMYK, JR. T. & SHEPPARD, D. E. (1977) Behavioral mutants of Drosophila melanogaster. Genetics 87, 9–128.

    Google Scholar 

  • HING, H. K., BANGALORE, L., SUN, X. & ARTAVANISTSAKONAS, S. (1999) Mutations in the heatshock cognate 70 protein (hsc4) modulate Notch signaling. Eur. J. Cell Biol. 78, 69–697.

    PubMed  Google Scholar 

  • HINSHAW, J. E. & SCHMID, S. L. (1995) Dynamin selfassembles into rings suggesting a mechanism for coated vesicle budding. Nature 374, 19–192.

    PubMed  Google Scholar 

  • HYMAN, J., CHEN, H., DI FIORE, P. P., DE CAMILLI, P. & BRUNGER, A. T. (2000) Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). J. Cell Biol. 149, 53–546.

    PubMed  Google Scholar 

  • IKEDA, K., OZAWA, S. & HAGIWARA, S. (1976) Synaptic transmission reversibly conditioned by single-gene mutation in Drosophila melanogaster. Nature 259, 48–491.

    PubMed  Google Scholar 

  • JAN, L. Y. & JAN, Y. N. (1976a) Properties of the larval neuromuscular junction in Drosophila melanogaster. J. Physiol. 262, 18–214.

    PubMed  Google Scholar 

  • JAN, L. Y. & JAN, Y. N. (1976b) L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction. J. Physiol. 262, 21–236.

    PubMed  Google Scholar 

  • JIA, X. X., GORCZYCA, M. & BUDNIK, V. (1994) Ultrastructure of neuromuscular junctions in Drosophila: Comparison of wild type and mutants with increased excitability. J. Neurobiol. 24, 102–1044.

    Google Scholar 

  • JOHANSEN, J., HALPERN, M. E., JOHANSEN, K. M. & KESHISHIAN, H. (1989) Stereotypic morphology of glutamatergic synapses on identified muscle cells of Drosophila larvae. J. Neurosci. 9, 71–725.

    PubMed  Google Scholar 

  • JORGENSEN, E. M., HARTWIEG, E., SCHUSKE, K., NONET, M. L., JIN, Y. & HORVITZ, H. R. (1995) Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans. Nature 378, 19–199.

    PubMed  Google Scholar 

  • KALTHOFF, C., ALVES, J., URBANKE, C., KNORR, R. & UNGEWICKELL, E. J. (2002) Unusual structural organization of the endocytic proteins AP180 and epsin 1. J. Biol. Chem. 277, 820–8216.

    PubMed  Google Scholar 

  • KAY, B. K., YAMABHAI, M., WENDLAND, B. & EMR, S. D. (1999) Identification of a novel domain shared by putative components of the endocytic and cytoskeletal machinery. Protein Sci. 8, 43–438.

    PubMed  Google Scholar 

  • KENNERDELL, J. R. & CARTHEW, R. W. (2000) Heritable gene silencing in Drosophila using double-stranded RNA. Nat. Biotechnol. 18, 89–898.

    PubMed  Google Scholar 

  • KESHISHIAN, H., CHIBA, A., CHANG, T. N., HALFON, M. S., HARKINS, E. W., JARECKI, J., WANG, L., ANDERSON, M., CASH, S., HALPERN, M. E. & JOHANSEN, J. (1993) Cellular mechanisms governing synaptic development in Drosophila melanogaster. J. Neurobiol. 24, 75–787.

    PubMed  Google Scholar 

  • KIM, J. A. & KIM, H. L. (2001) Cell-free expression and functional reconstitution of CALM in clathrin assembly. Exp. Mol. Med. 33, 8–94.

    PubMed  Google Scholar 

  • KIM, W. T., CHANG, S., DANIELL, L., CREMONA, O., DI PAOLO, G. & DE CAMILLI, P. (2002) Delayed reentry of recycling vesicles into the fusion-competent synaptic vesicle pool in synaptojanin 1 knockout mice. Proc. Natl. Acad. Sci. USA 99, 1714–17148.

    PubMed  Google Scholar 

  • KIRCHHAUSEN, T. (1999) Adaptors for clathrin-mediated traffic. Annu. Rev. Cell Dev. Biol. 15, 70–732.

    PubMed  Google Scholar 

  • KITAMOTO, T. (2001) Conditional modification of behavior in Drosophila by targeted expression of a temperature sensitive shibire allele in defined neurons. J. Neurobiol. 47, 8–92.

    PubMed  Google Scholar 

  • KLINGAUF, J., KAVALALI, E. T. & TSIEN, R. W. (1998) Kinetics and regulation of fast endocytosis at hippocampal synapses. Nature 394, 58–585.

    PubMed  Google Scholar 

  • KOENIG, J. H. & IKEDA, K. (1989) Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval. J. Neurosci. 9, 384–3860.

    PubMed  Google Scholar 

  • KOENIG, J. H. & IKEDA, K. (1996) Synaptic vesicles have two distinct recycling pathways. J. Cell Biol. 135, 79–808.

    PubMed  Google Scholar 

  • KOENIG, J. H. & IKEDA, K. (1999) Contribution of active zone subpopulation of vesicles to evoked and spontaneous release. J. Neurophysiol. 81, 149–1505.

    PubMed  Google Scholar 

  • KOENIG, J. H., SAITO, K. & IKEDA, K. (1983) Reversible control of synaptic transmission in a single gene mutant of Drosophila melanogaster. J. Cell Biol. 96, 151–1522.

    PubMed  Google Scholar 

  • KOHTZ, D. S. & PUSZKIN, S. (1988) A neuronal protein (NP185) associated with clathrin-coated vesicles. Characterization of NP185 with monoclonal antibodies. J. Biol. Chem. 263, 741–7425.

    PubMed  Google Scholar 

  • KOSAKA, T. & IKEDA, K. (1983a) Possible temperaturedependent blockage of synaptic vesicle recycling induced by a single gene mutation in Drosophila. J. Neurobiol. 14, 20–225.

    PubMed  Google Scholar 

  • KOSAKA, T. & IKEDA, K. (1983b) Reversible blockage of membrane retrieval and endocytosis in the garland cell of the temperature-sensitive mutant of Drosophila melanogaster, shibire ts1. J. Cell Biol. 97, 49–507.

    PubMed  Google Scholar 

  • KRISHNAN, K. S., RIKHY, R., RAO, S., SHIVALKAR, M., MOSKO, M., NARAYANAN, R., ETTER, P., ESTES, P. S. & RAMASWAMI, M. (2001) Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Neuron 30, 19–210.

    PubMed  Google Scholar 

  • KUROMI, H. & KIDOKORO, Y. (1998) Two distinct pools of synaptic vesicles in single presynaptic boutons in a temperature-sensitive Drosophila mutant, shibire. Neuron 20, 91–925.

    PubMed  Google Scholar 

  • KUROMI, H. & KIDOKORO, Y. (1999) The optically determined size of exo/endo cycling vesicle pool correlates with the quantal content at the neuromuscular junction of Drosophila larvae. J. Neurosci. 19, 155–1565.

    PubMed  Google Scholar 

  • LEE, E., MARCUCCI, M., DANIELL, L., PYPAERT, M., WEISZ, O. A., OCHOA, G. C., FARSAD, K., WENK, M. R. & DE CAMILLI, P. (2002) Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 297, 119–1196.

    PubMed  Google Scholar 

  • LEVENTIS, P. A., CHOW, B. M., STEWART, B. A., IYENGAR, B., CAMPOS, A. R. & BOULIANNE, G. L. (2001) Drosophila Amphiphysin is a post-synaptic protein required for normal locomotion but not endocytosis. Traffic 2, 83–850.

    PubMed  Google Scholar 

  • LINDNER, R. & UNGEWICKELL, E. (1992) Clathrin associated proteins of bovine brain coated vesicles. An analysis of their number and assembly-promoting activity. J. Biol. Chem. 267, 1656–16573.

    PubMed  Google Scholar 

  • LITTLETON, J. T., BAI, J., VYAS, B., DESAI, R., BALTUS, A. E., GARMENT, M. B., CARLSON, S. D., GANETZKY, B. & CHAPMAN, E. R. (2001) Synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+-triggered fusion and recycling of synaptic vesicles in vivo. J. Neurosci. 21, 142–1433.

    PubMed  Google Scholar 

  • LITTLETON, J. T., STERN, M., SCHULZE, K., PERIN, M. & BELLEN, H. J. (1993) Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca2+-activated neurotransmitter release. Cell 74, 112–1134.

    PubMed  Google Scholar 

  • LOEWEN, C. A., MACKLER, J. M. & REIST, N. E. (2001) Drosophila synaptotagmin I null mutants survive to early adulthood. Genesis 31, 3–36.

    PubMed  Google Scholar 

  • LUTHI, A., DI PAOLO, G., CREMONA, O., DANIELL, L., DE CAMILLI, P. & MCCORMICK, D. A. (2001) Synaptojanin 1 contributes to maintaining the stability of GABAergic transmission in primary cultures of cortical neurons. J. Neurosci. 21, 910–9111.

    PubMed  Google Scholar 

  • MACKLER, J. M., DRUMMOND, J. A., LOEWEN, C. A., ROBINSON, I. M. & REIST, N. E. (2002) TheC2BCa2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature 418, 34–344.

    PubMed  Google Scholar 

  • MAO, Y., CHEN, J., MAYNARD, J. A., ZHANG, B. & QUIOCHO, F. A. (2001) A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis. Cell 104, 43–440.

    PubMed  Google Scholar 

  • MAREK, K. W. & DAVIS, G. W. (2002) Transgenically encoded protein photoinactivation (FlAsH-FALI): Acute inactivation of synaptotagmin I. Neuron 36, 80–813.

    PubMed  Google Scholar 

  • MARTIN, T. F. (2001) PI(4,5)P(2) regulation of surface membrane traffic. Curr. Opin. Cell Biol. 13, 49–499.

    PubMed  Google Scholar 

  • MCGUIRE, S. E., LE, P. T. & DAVIS, R. L. (2001) The role of Drosophila mushroom body signaling in olfactory memory. Science 293, 133–1333.

    PubMed  Google Scholar 

  • MCMAHON, H. T., WIGGE, P. & SMITH, C. (1997) Clathrin interacts specifically with amphiphysin and is displaced by dynamin. FEBS Lett. 413, 31–322.

    PubMed  Google Scholar 

  • MCPHERSON, P. S., GARCIA, E. P., SLEPNEV, V. I., DAVID, C., ZHANG, X., GRABS, D., SOSSIN, W. S., BAUERFEIND, R., NEMOTO, Y. & DE CAMILLI, P. (1996) A presynaptic inositol-5-phosphatase. Nature 379, 35–357.

    PubMed  Google Scholar 

  • MICHEVA, K. D., RAMJAUN, A. R., KAY, B. K. & MCPHERSON, P. S. (1997) SH3 domain-dependent interactions of endophilin with amphiphysin. FEBS Lett. 414, 30–312.

    PubMed  Google Scholar 

  • MILLER, T. M. & HEUSER, J. E. (1984) Endocytosis of synaptic vesicle membrane at the frog neuromuscular junction. J. Cell Biol. 98, 68–698.

    PubMed  Google Scholar 

  • MORGAN, J. R., AUGUSTINE, G. J. & LAFER, E. M. (2002) Synaptic vesicle endocytosis: The races, places, and molecular faces. Neuromolecular Med. 2, 10–114.

    PubMed  Google Scholar 

  • MORGAN, J. R., PRASAD, K., HAO, W., AUGUSTINE, G. J. & LAFER, E. M. (2000) A conserved clathrin assembly motif essential for synaptic vesicle endocytosis. J. Neurosci. 20, 866–8676.

    PubMed  Google Scholar 

  • MORGAN, J. R., PRASAD, K., JIN, S., AUGUSTINE, G. J. & LAFER, E.M. (2001) Uncoating of clathrin-coated vesicles in presynaptic terminals: Roles for Hsc70 and auxilin. Neuron 32, 28–300.

    PubMed  Google Scholar 

  • MORGAN, J. R., ZHAO, X., WOMACK, M., PRASAD, K., AUGUSTINE, G. J. & LAFER, E. M. (1999) A role for the clathrin assembly domain of AP180 in synaptic vesicle endocytosis. J. Neurosci. 19, 1020–10212.

    PubMed  Google Scholar 

  • MURPHY, J. E., PLEASURE, I. T., PUSZKIN, S., PRASAD, K. & KEEN, J. H. (1991) Clathrin assembly protein AP-3. The identity of the 155K protein, AP 180, and NP185 and demonstration of a clathrin binding domain. J. Biol. Chem. 266, 440–4408.

    PubMed  Google Scholar 

  • MURTHY, V. N. & STEVENS, C. F. (1998) Synaptic vesicles retain their identity through the endocytic cycle. Nature 392, 49–501.

    PubMed  Google Scholar 

  • NEWMYER, S. L. & SCHMID, S. L. (2001) Dominant interfering Hsc70 mutants disrupt multiple stages of the clathrin-coated vesicle cycle in vivo. J. Cell Biol. 152, 60–620.

    PubMed  Google Scholar 

  • NONET, M. L., HOLGADO, A. M., BREWER, F., SERPE, C. J., NORBECK, B. A., HOLLERAN, J., WEI, L., HARTWIEG, E., JORGENSEN, E. M. & ALFONSO, Molecular mechanisms of synaptic vesicle recycling 587 A. (1999) UNC-11, a Caenorhabditis elegans AP180 homologue, regulates the size and protein composition of synaptic vesicles. Mol. Biol. Cell 10, 234–2360.

  • OSTERWALDER, T., YOON, K. S., WHITE, B. H. & KESHISHIAN, H. (2001) A conditional tissue-specific transgene expression system using inducible GAL4. Proc. Natl. Acad. Sci. USA 98, 1259–12601.

    PubMed  Google Scholar 

  • PALFREY, H. C. & ARTALEJO, C. R. (1998) Vesicle recycling revisited: Rapid endocytosis may be the first step. Neuroscience 83, 96–989.

    PubMed  Google Scholar 

  • PEARSE, B. M. (1976) Clathrin: A unique protein associated with intracellular transfer of membrane by coated vesicles. Proc. Natl. Acad. Sci. USA 73, 125–1259.

    PubMed  Google Scholar 

  • PERIN, M. S., JOHNSTON, P. A., OZCELIK, T., JAHN, R., FRANCKE, U. & SUDHOF, T. C. (1991) Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans. J. Biol. Chem. 266, 61–622.

    PubMed  Google Scholar 

  • PETROVICH, T. Z., MERAKOVSKY, J. & KELLY, L. E. (1993) Agenetic analysis of the stoned locus and its interaction with dunce, shibire and Suppressor of stoned variants of Drosophila melanogaster. Genetics 133, 95–965.

    PubMed  Google Scholar 

  • PHILLIPS, A. M., SMITH, M., RAMASWAMI, M. & KELLY, L. E. (2000) The products of the Drosophila stoned locus interact with synaptic vesicles via synaptotagmin. J. Neurosci. 20, 825–8261.

    PubMed  Google Scholar 

  • PISHVAEE, B., COSTAGUTA, G., YEUNG, B. G., RYAZANTSEV, S., GREENER, T., GREENE, L. E., EISENBERG, E., MCCAFFERY, J. M. & PAYNE, G. S. (2000) A yeast DNA J protein required for uncoating of clathrin-coated vesicles in vivo. Nat. Cell Biol. 2, 95–963.

    PubMed  Google Scholar 

  • PLOMANN, M., LANGE, R., VOPPER, G., CREMER, H., HEINLEIN, U. A., SCHEFF, S., BALDWIN, S. A., LEITGES, M., CRAMER, M., PAULSSON, M. & BARTHELS, D. (1998) PACSIN, a brain protein that is upregulated upon differentiation into neuronal cells. Eur. J. Biochem. 256, 20–211.

    PubMed  Google Scholar 

  • QUALMANN, B., ROOS, J., DIGREGORIO, P. J. & KELLY, R. B. (1999) Syndapin I, a synaptic dynaminbinding protein that associates with the neural Wiskott-Aldrich syndrome protein. Mol. Biol. Cell. 10, 50–513.

    PubMed  Google Scholar 

  • RAMASWAMI, M., KRISHNAN, K. S. & KELLY, R. B. (1994) Intermediates in synaptic vesicle recycling revealed by optical imaging of Drosophila neuromuscular junctions. Neuron 13, 36–375.

    PubMed  Google Scholar 

  • RAZZAQ, A., ROBINSON, I. M., MCMAHON, H. T., SKEPPER, J. N., SU, Y., ZELHOF, A. C., JACKSON, A. P., GAY, N. J. & O'KANE, C. J. (2001) Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila. Genes Dev. 15, 296–2979.

    PubMed  Google Scholar 

  • REIST, N. E., BUCHANAN, J., LI, J., DIANTONIO, A., BUXTON, E. M. & SCHWARZ, T. L. (1998) Morphologically docked synaptic vesicles are reduced in synaptotagmin mutants of Drosophila. J. Neurosci. 18, 766–7673.

    PubMed  Google Scholar 

  • RICHARDS, D. A., GUATIMOSIM, C. & BETZ, W. J. (2000) Two endocytic recycling routes selectively fill two vesicle pools in frog motor nerve terminals. Neuron 27, 55–559.

    PubMed  Google Scholar 

  • RINGSTAD, N., NEMOTO, Y. & DE CAMILLI, P. (1997) The SH3p4/Sh3p8/SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain. Proc. Natl. Acad. Sci. USA 94, 856–8574.

    PubMed  Google Scholar 

  • RINGSTAD, N., GAD, H., LOW, P., DI PAOLO, G., BRODIN, L., SHUPLIAKOV, O. & DE CAMILLI, P. (1999) Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron 24, 14–154.

    PubMed  Google Scholar 

  • RIKHY, R., KUMAR, V., MITTAL, R. & KRISHNAN, K. S. (2002) Endophilin is critically required for synapse formation and function in Drosophila melanogaster. J. Neurosci. 22, 747–7484.

    PubMed  Google Scholar 

  • ROBINSON, M. S. (1994) The role of clathrin, adaptors and dynamin in endocytosis. Curr. Opin. Cell Biol. 6, 53–544.

    PubMed  Google Scholar 

  • ROMAN, G., ENDO, K., ZONG, L. & DAVIS, R. (2001) P[Switch], a system for spatial and temporal control of gene expression in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 98, 1260–12607.

    PubMed  Google Scholar 

  • RONG, Y. S. & GOLIC, K. G. (2000) Gene targeting by homologous recombination in Drosophila. Science 288, 201–2018.

    PubMed  Google Scholar 

  • ROOS, J. & KELLY, R. B. (1998) Dap160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin. J. Biol Chem. 273, 1910–19119.

    PubMed  Google Scholar 

  • ROOS, J. & KELLY, R. B. (1999) The endocytic machinery in nerve terminals surrounds sites of exocytosis. Curr. Biol. 9, 141–1414.

    PubMed  Google Scholar 

  • RORTH, P. (1996) A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. Proc. Natl. Acad. Sci. USA 93, 1241–12422.

    PubMed  Google Scholar 

  • ROTH, T, F. & PORTER, K. R. (1964) Yolk protein uptake in the oocyte of the mosquito Aedes aegypti. J. Cell Biol. 20, 31–332.

    PubMed  Google Scholar 

  • RYAN, T. A., REUTER, H., WENDLAND, B., SCHWEIZER, F. E., TSIEN, R. W. & SMITH, S. J. (1993) The kinetics of synaptic vesicle recycling measured at single presynaptic boutons. Neuron 11, 71–724.

    PubMed  Google Scholar 

  • SALCINI, A. E., HILLIARD, M. A., CROCE, A., ARBUCCI, S., LUZZI, P., TACCHETTI, C., DANIELL, L., DE CAMILLI, P., PELICCI, P. G., DI FIORE, P. P. & BAZZICALUPO, P. (2001) The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling. Nat. Cell Biol. 3, 75–760.

    PubMed  Google Scholar 

  • SANKARANARAYANAN, S. & RYAN, T. A. (2000) Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nat. Cell Biol. 2, 19–204.

    PubMed  Google Scholar 

  • SCHLOSSMAN, D. M., SCHMID, S. L., BRAELL, W. A. & ROTHMAN, J. E. (1984) An enzyme that removes clathrin coats: Purification of an uncoating ATPase. J. Cell Biol. 99, 72–733.

    PubMed  Google Scholar 

  • SCHMID, S. L. & ROTHMAN J. E. (1985) Enzymatic dissociation of clathrin cages in a two-stage process. J. Biol. Chem. 260, 1004–10049.

    PubMed  Google Scholar 

  • SCHMID, S. L., MCNIVEN, M. A. & DE CAMILLI, P. (1998) Dynamin and its partners:A progress report. Curr. Opin. Cell Biol. 10, 50–512.

    PubMed  Google Scholar 

  • SEVER, S., DAMKE, H. & SCHMID SL. (2000a) Dynamin: GTP controls the formation of constricted coated pits, the rate limiting step in clathrin-mediated endocytosis. J. Cell Biol. 150, 113–1148.

    PubMed  Google Scholar 

  • SEVER, S., DAMKE, H. & SCHMID SL. (2000b) Garrotes, springs, ratchets, and whips: Putting dynamin models to the test. Traffic 1, 38–392.

    PubMed  Google Scholar 

  • SHPETNER, H. S. & VALLEE, R. B. (1989) Identification of dynamin, a novel mechanochemical enzyme that mediates interactions between microtubules. Cell 59, 42–432.

    PubMed  Google Scholar 

  • SHPETNER, H. S., HERSKOVITS, J. S. & VALLEE, R. B. (1996) A binding site for SH3 domains targets dynamin to coated pits. J. Biol. Chem. 271, 1–16.

    PubMed  Google Scholar 

  • SHUPLIAKOV, O., LOW, P., GRABS, D., GAD, H., CHEN, H., DAVID, C., TAKEI, K., DE CAMILLI, P. & BRODIN, L. (1997) Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions. Science 276, 25–263.

    PubMed  Google Scholar 

  • SIDDIQI, O. & BENZER, S. (1976) Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 73, 325–3257.

    PubMed  Google Scholar 

  • SIMPSON, F., PEDEN, A. A., CHRISTOPOULOU, L. & ROBINSON, M. S. (1997) Characterization of the adaptor-related protein complex, AP-3. J. Cell Biol. 137, 83–845.

    PubMed  Google Scholar 

  • SINGER-KRUGER, B., NEMOTO, Y., DANIELL, L., FERRO-NOVICK, S. & DE CAMILLI, P. (1998) Synaptojanin family members are implicated in endocytic membrane traffic in yeast. J. Cell Sci. 111, 334–3356.

    PubMed  Google Scholar 

  • STEFAN, C. J., AUDHYA, A. & EMR, S. D. (2002) The yeast synaptojanin-like proteins control the cellular distribution of phosphatidylinositol (4,5)-bisphosphate. Mol. Biol. Cell 13, 54–557.

    PubMed  Google Scholar 

  • STEVENS, C. F. & WILLIAMS, J. H. (2000) "Kiss and run" exocytosis at hippocampal synapses. Proc. Natl. Acad. Sci. USA 97, 1282–12833.

    PubMed  Google Scholar 

  • STEWART, B. A., ATWOOD, H. L., RENGER, J. J., WANG, J. & WU, C. F. (1994) Improved stability of Drosophila larval neuromuscular preparations in haemolymph-like physiological solutions. J. Comp. Physiol. [A]. 175, 17–191.

    Google Scholar 

  • STIMSON, D. T., ESTES, P. S., RAO, S., KRISHNAN, K. S., KELLY, L. E. & RAMASWAMI, M. (2001) Drosophila stoned proteins regulate the rate and fidelity of synaptic vesicle internalization. J. Neurosci. 21, 303–3044.

    PubMed  Google Scholar 

  • STIMSON, D. T., ESTES, P. S., SMITH, M., KELLY, L. E. & RAMASWAMI, M. (1998) A product of the Drosophila stoned locus regulates neurotransmitter release. J. Neurosci. 18, 963–9649.

    PubMed  Google Scholar 

  • SUDHOF, T. C. & RIZO, J. (1996) Synaptotagmins: C2-domain proteins that regulate membrane traffic. Neuron 17, 37–388.

    PubMed  Google Scholar 

  • SUN, J. Y., WU, X. S. & WU, L. G. (2002) Single and multiple vesicle fusion induce different rates of endocytosis at a central synapse. Nature 417, 55–559.

    PubMed  Google Scholar 

  • SWEITZER, S. M. & HINSHAW, J. E. (1998) Dynamin undergoes a GTP-dependent conformational change causing vesiculation. Cell 93, 102–1029.

    PubMed  Google Scholar 

  • TAKEI, K., MCPHERSON, P. S., SCHMID, S. L. & DE CAMILLI, P. (1995) Tubular membrane invaginations coated by dynamin rings are induced by GTP-gamma S in nerve terminals. Nature 374, 18–190.

    PubMed  Google Scholar 

  • TAKEI, K., MUNDIGL, O., DANIELL, L. & DE CAMILLI, P. (1996) The synaptic vesicle cycle: A single vesicle budding step involving clathrin and dynamin. J. Cell Biol. 133, 123–1250.

    PubMed  Google Scholar 

  • TEBAR, F., BOHLANDER, S. K. & SORKIN, A. (1999) Clathrin assembly lymphoid myeloid leukemia (CALM) protein: Localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic. Mol. Biol. Cell 10, 268– 2702.

    PubMed  Google Scholar 

  • TENG, H. & WILKINSON, R. S. (2000) Clathrin-mediated endocytosis near active zones in snake motor boutons. J. Neurosci. 20, 798–7993.

    PubMed  Google Scholar 

  • TRAUB, L. M., DOWNS, M. A., WESTRICH, J. L. & FREMONT, D. H. (1999) Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly. Proc. Natl. Acad. Sci. USA 96, 890–8912.

    PubMed  Google Scholar 

  • 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, 89–907.

    PubMed  Google Scholar 

  • UNGEWICKELL, E., UNGEWICKELL, H., HOLSTEIN, S. E., LINDNER, R., PRASAD, K., BAROUCH, W., MARTIN, B., GREENE L. E. & EISENBERG, E. (1995) Role of auxilin in uncoating clathrin-coated vesicles. Nature 378, 63–635.

    PubMed  Google Scholar 

  • VAN DER BLIEK, A. M. & MEYEROWITZ, E. M. (1991) Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 351, 41–414.

    PubMed  Google Scholar 

  • VON GERSDORFF, H. & MATTHEWS, G. (1994) Dynamics of synaptic vesicle fusion and membrane retrieval in synaptic terminals. Nature 367, 73–739.

    PubMed  Google Scholar 

  • VERSTREKEN, P., KJAERULFF, O., LLOYD, T. E., ATKINSON, R., ZHOU, Y., MEINERTZHAGEN, I. A. & BELLEN, H. J. (2002) Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release. Cell 109, 10–112.

    PubMed  Google Scholar 

  • WADDELL, S., ARMSTRONG, J. D., KITAMOTO, T., KAISER, K. & QUINN, W. G. (2000) The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory. Cell 103, 80–813.

    PubMed  Google Scholar 

  • WENDLAND, B., STEECE, K. E. & EMR, S. D. (1999) Yeast epsins contain an essential N-terminal ENTH domain, bind clathrin and are required for endocytosis. EMBO J. 18, 438–4393.

    PubMed  Google Scholar 

  • WIGGE, P., VALLIS, Y. & MCMAHON, H. T. (1997) Inhibition of receptor-mediated endocytosis by the amphiphysin SH3 domain. Curr Biol. 7, 55–560.

    PubMed  Google Scholar 

  • YAMABHAI, M., HOFFMAN, N. G., HARDISON, N. L., MCPHERSON, P. S., CASTAGNOLI, L., CESARENI, G. & KAY, B. K. (1998) Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains. J. Biol. Chem. 273, 3140–31407.

    PubMed  Google Scholar 

  • YE, W. & LAFER, E. M. (1995a) Bacterially expressed F1-20/AP-3 assembles clathrin into cages with a narrowsize distribution: Implications for the regulation of quantal size during neurotransmission. J. Neurosci Res. 41, 1–26.

    PubMed  Google Scholar 

  • YE, W. & LAFER, E. M. (1995b) Clathrin binding and assembly activities of expressed domains of the synapsespecific clathrin assembly protein AP-3. J. Biol. Chem. 270, 1093–10939.

    PubMed  Google Scholar 

  • ZAREMBA, S. & KEEN, J. H. (1983) Assembly polypeptides from coated vesicles mediate reassembly of unique clathrin coats. J. Cell Biol. 97, 133–1347.

    PubMed  Google Scholar 

  • ZELHOF, A. C., BAO, H., HARDY, R. W., RAZZAQ, A., ZHANG, B. & DOE, C. Q. (2001) Drosophila Amphiphysin is implicated in protein localization and membrane morphogenesis but not in synaptic vesicle endocytosis. Development 128, 500–5015.

    PubMed  Google Scholar 

  • ZENISEK, D., STEYER, J. A., FELDMAN, M. E. & ALMERS, W. (2002) A membrane marker leaves synaptic vesicles inmilliseconds after exocytosis in retinal bipolar cells. Neuron 35, 108–1097

    PubMed  Google Scholar 

  • ZHANG, B., GANETZKY, B., BELLEN, H. J. & MURTHY, V. N. (1999) Tailoring uniform coats for synaptic vesicles during endocytosis. Neuron 23, 41–422.

    PubMed  Google Scholar 

  • ZHANG, B., KOH, Y. H., BECKSTEAD, R. B., BUDNIK, V., GANETZKY, B. & BELLEN, H. J. (1998) Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis. Neuron 21, 146–1475.

    PubMed  Google Scholar 

  • ZHANG, B. & RAMASWAMI, M. (1999) Synaptic vesicle endocytosis and recycling. In Frontiers in Molecular Biology: Neurotransmitter Release edited by H. J. BELLEN pp. 38–431, London, Oxford University Press.

    Google Scholar 

  • ZHANG, B. & ZELHOF, A. C. (2002) Amphiphysins: Raising theBARfor synaptic vesicle recycling and membrane dynamics. Traffic 3, 45–460.

    PubMed  Google Scholar 

  • ZHANG, J. Z., DAVLETOV, B. A., SUDHOF, T. C. & ANDERSON, R. G. (1994) Synaptotagmin I is a high affinity receptor for clathrin AP-2: Implications for membrane recycling. Cell 78, 75–760.

    PubMed  Google Scholar 

  • ZHOU, S., SOUSA, R., TANNERY, N. H. & LAFER, E. M. (1992) Characterization of a novel synapse-specific protein. II. cDNA cloning and sequence analysis of the F1-20 protein. J. Neurosci. 12, 214–2155.

    PubMed  Google Scholar 

  • 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, 97–980.

    PubMed  Google Scholar 

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Zhang, B. Genetic and molecular analysis of synaptic vesicle recycling in Drosophila . J Neurocytol 32, 567–589 (2003). https://doi.org/10.1023/B:NEUR.0000020611.44254.86

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