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研究生:黃建彰
研究生(外文):Chien-Chang Huang
論文名稱:Rab3A在分泌過程中所扮演角色之研究
論文名稱(外文):Study of the role of Rab3A in the secretory pathway
指導教授:高閬仙高閬仙引用關係
指導教授(外文):Lung-Sen Kao
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:134
中文關鍵詞:胞吐作用全內反射螢光顯微鏡囊泡
外文關鍵詞:Rab3AMunc13-1Munc18-1exocytosisTIRFMvesicle
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Rab3A是小G蛋白質家族成員之一,參與在胞吐作用晚期的過程之中,包含docking、priming與fusion。然而,在胞吐作用晚期的過程中對於Rab3A實際參與的步驟與功能是不清楚的。過去研究指出,在細胞膜的附近,Rab3A/RIM /Munc13-1形成三合一的複合物被認為用作調控分泌性囊泡priming的過程。Phorbol ester,PMA可以增加細胞內priming囊泡的數目,它會直接活化Munc13-1的作用與間接的透過PKC活化Munc18-1來調控syntaxin 1a促使囊泡priming增加。在研究中我們透過PMA在PC12細胞中對ATP所誘發胞吐作用的影響,藉此來研究Rab3A、Munc13-1與Munc18-1間可能作用的分子機制。PMA的刺激增加ATP誘導囊泡分泌的活性與加速囊泡分泌運動的速度。根據我們的研究顯示在表現不同Rab3A及其突變蛋白的細胞中,PMA的作用效應產生不同的差異。在Rab3A-knockdown的細胞中表現Munc13-1,完全的抑制分泌作用的進行,這個抑制的效應可以因表現不會與RIM結合的Munc13-1突變(128-Munc13-1)所回復。在表現128-Munc13-1的細胞中,Rab3A對分泌的抑制效應消失;PMA的作用效應因為GTP-Rab3A (Q81L)表現而被抑制,且這個抑制作用能被Munc18-1表現所回復。在表現Munc18-1細胞中,Rab3A的活性對分泌作用的調控效應消失;由於Munc18-1會與Rab3A產生交互作用,在ATP刺激之下促進Rab3A從囊泡膜的表面解離。總和上述結果,Rab3A 在GTP/GDP間轉換循環透過RIM來參與活化Munc13-1;Munc18-1作用在Rab3A/RIM/Munc13-1的下游,調控syntaxin 1a結構,幫助囊泡priming。最後,Munc18-1促進Rab3A從囊泡膜上解離,促成囊泡分泌的發生。
Rab3A is a small G protein of Rab family that involves in the late steps of exocytosis, including docking, priming and fusion. However, it is not clear at which step of exocytic pathway that Rab3A actually acts. Near the plasma membrane, Rab3A/RIM/Munc13-1 form a tripartite complex which is thought to regulate the priming of secretory vesicles. Phorbol ester, PMA, is known to increase the number of primed vesicles. It activates PKC-independent Munc13-1 activation and PKC- dependent Munc18-1-mediated interaction with syntaxin 1a to enhance vesicle priming. In this study, we examined the effects of PMA on ATP-stimulated exocytosis in PC12 cells to study the possible molecular interactions among Rab3A, Munc13-1 and Munc18-1. PMA enhanced the ATP-induced vesicular release and accelerated the kinetics of vesicle release. Our results show the effects of PMA varied in cells overexpressing Rab3A and its mutants. In Rab3A-knockdown cells, overexpression of Munc13-1 inhibited the secretion completely and the inhibition was rescued by RIM-binding deficient Munc13-1 mutant, 128-Munc13-1. In 128-Munc13-1 overexpressing cells, the effects of Rab3A on secretion was abolished and the effect of PMA disappeared in cells overexpressing GTP-Rab3A (Q81L) which could be reversed by co-expressing Munc18-1. In cells overexpressing Munc18-1, manipulation of Rab3A activity had no effect on secretion. Munc18-1 was shown to interact with Rab3A and promoted the disassociation of Rab3A upon ATP stimulation. In summary, the Rab3A cycle is coupled with the activation of Munc13-1 via RIM, which accounts for the regulation of secretion by Rab3A. Munc18-1 acts downstream of Munc13-1/RIM/Rab3A and interacts with syntaxin 1a allowing vesicle priming. Furthermore, Munc18-1 promotes Rab3A dissociation from the vesicles, which then results in fusion.
Abbreviations…………………………………………………………………………4
Chinese abstract………………………...……………………………………………5
English abstract………………………...…………………………………………….6
Introduction…………………………………………………………………………..7
1. The function of Rab3 in the late steps of exocytosis……………………………..8
2. RIM involves in vesicle priming to form the protein scaffold at active zone…10
3. Munc13 is served as a vesicle priming factor and is essential for vesicle release.10
4. SNAREs: The candidate proteins promote membrane fusion…………………...11
5. Munc18 interacts with syntaxin 1a and controls the formation
of SNARE complex………..……………………………………………………..12
6. Ca2+ regulation and exocytosis……………………………………………….…13
7. The model system of exocytosis: PC12 cells (rat pheochromocytoma)………..13
8. Aims of the study……………………………………………………………….14
Materials and Methods……………………………………………………………..15
1. Materials………………………………………………………………………...15
2. Plasmids………………………………………………………………………...15
3. Cell culture and Transfection…………………………………………………...16
4. Knockdown of Rab3A…………………………………………………………..16
5. Stimulation of PC12 cells……………………………………………………….17
6. Immunocytochemistry and Confocal imaging………………………………….17
7. TIRF imaging………………………………………..…………………………...18
8. Photobleaching………………………………………..………………………….19
9. Image analysis…………………………………………..………………………..19
10. Amperometry……………………………………………………………………..20
Results……………………………………………………………………………….21
1. The subcellular localization of Rab3A and large dense-core vesicles…..…….…21
2. Changes of fluorescence on NPY-EGFP-labeled vesicles upon
stimulation – analysis by TIRF microscope……………………..………….……21
3. Changes of fluorescence on EGFP-Rab3A-labeled vesicles upon
stimulation – analysis by TIRF microscope…………………………………….24
4. Effects of GTP hydrolysis and the effector protein, rabphilin, on Rab3A
dissociation………………………………………………...……………………..25
5. Effects of PMA on ATP-induced vesicle release in PC12 cells………………...27
6. Rab3A involved in PMA-induced vesicle priming………………………………28
7. Rab3A interacts with Munc13-1 via RIM during exocytosis…………………….29
8. Munc18-1 is at the downstream of Rab3A and Munc13-1 interaction to regulate
vesicle priming…………………………………………………………………...31
9. Munc18-1 promotes Rab3A dissociation from vesicle membrane…………….33
10. Rab3A interacts with Munc18-1 in PC12 cells…………………………………..34
Discussion……………………………………………………………………………36
1. The behavior of NPY-EGFP-labeled vesicle release upon stimulation
in PC12 cells………………………………………………………………………36
2. GTP hydrolysis of Rab3A is required for Rab3A dissociation
and vesicle release…………………………………………………………………37
3. The role of Rab3A in PMA-enhanced vesicle fusion……………………………...39
4. The role of Rab3A in modulating Munc13-1-dependent
PMA-enhanced exocytosis………………………………………………………...40
5. Munc18-1 plays dual roles in PMA-enhanced exocytosis……………………….41
6. Working hypothesis of the molecular mechanism that occurs
in the late stage of exocytosis……………………………………………………...42
Reference…………………………………………………………………………….43
Figures……………………………………………………………………………….55
Supplemental Materials…………………………………………………………….95
Appendix…………………………………………………………………………….97
1. Visualization of Rab3A dissociation during exocytosis: A study by total internal
reflection microscopy
2. Involvement of Rab3A in vesicle priming during exocytosis: interaction with
Munc13-1 and Munc18-1

Augustin, I., Betz, A., Herrmann, C., Jo, T., Brose, N. (1999a) Differential expression of two novel Munc13 proteins in rat brain. Biochem J. 337:363-371.

Augustin, I., Rosenmund, C., Südhof, T. C., Brose, N. (1999b) Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature. 400:457-461.

Ashery, U., Varoqueaux, F., Voets, T., Betz, A., Thakur, P., Koch, H., Neher, E., Brose, N., Rettig, J. (2000) Munc13-1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells. EMBO J. 19:3586-3596.

Bajjalieh, S. M. and Scheller, R. H. (1995) The biochemistry of neurotransmitter secretion. J Biol Chem. 270:1971-1974.

Barg, S., Olofsson, C. S., Schriever-Abeln, J., Wendt, A., Gebre-Medhin, S., Renstrom, E., Rorsman, P. (2002) Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells. Neuron. 33:287-299.

Basu, J., Shen, N., Dulubova, I., Lu, J., Guan, R., Guryev, O., Grishin, N. V., Rosenmund, C., Rizo, J. (2005) A minimal domain responsible for Munc13 activity. Nat Struct Mol Biol. 12:1017-1018.

Betz, A., Ashery, U., Rickmann, M., Augustin, I., Neher, E., Südhof, T. C., Rettig, J., Brose, N. (1998) Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release. Neuron. 21:123-136.
Betz, A., Thakur, P., Junge, H. J., Ashery, U., Rhee, J. S., Scheuss, V., Rosenmund, C., Rettig, J., Brose, N. (2001) Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 30:183-196.

Brose, N., Hofmann, K., Hata, Y., Südhof, T. C. (1995) Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins. J Biol Chem. 270:25273-25280.

Chen, Y. A., Scheller, R. H. (2001) SNARE-mediated membrane fusion. Nat Rev Mol Cell Biol. 2:98-106.

Chou, J. H., Jahn, R. (2000) Binding of Rab3A to synaptic vesicles. J Biol Chem. 275:9433-9440.

Chung, S. H., Takai, Y., Holz, R. W. (1995) Evidence that the Rab3a-binding protein, rabphilin3a, enhances regulated secretion. Studies in adrenal chromaffin cells. J Biol Chem. 270:16714-16718.

Chung, S. H., Joberty, G., Gelino, E. A., Macara, I. G., Holz, R. W. (1999) Comparison of the effects on secretion in chromaffin and PC12 cells of Rab3 family members and mutants. Evidence that inhibitory effects are independent of direct interaction with Rabphilin3. J Biol Chem. 274:18113-18120.

Coppola, T., Hirling, H., Perret-Menoud, V., Gattesco, S., Catsicas, S., Joberty, G., Macara, I. G., Regazzi, R. (2001a) Rabphilin dissociated from Rab3 promotes endocytosis through interaction with Rabaptin-5. J Cell Sci. 114:1757-1764.
Coppola, T., Magnin-Luthi, S., Perret-Menoud, V., Gattesco, S., Schiavo, G., Regazzi, R. (2001b) Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem. 276:32756-32762.

Deák, F., Xu, Y., Chang, W. P., Dulubova, I., Khvotchev, M., Liu, X., Südhof, T. C., Rizo, J. (2009) Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. J Cell Biol. 184:751-764.

Diao, J., Su Z., Lu X., Yoon T. Y., Shin Y. K., Ha T. (2010) Single-Vesicle Fusion Assay Reveals Munc18-1 Binding to the SNARE Core Is Sufficient for Stimulating Membrane Fusion. ACS Chem Neurosci. 1:168-174.

Dulubova, I., Lou, X., Lu, J., Huryeva, I., Alam, A., Schneggenburger, R., Südhof, T. C., Rizo, J. (2005) A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity? EMBO J. 24:2839-2850.

Dulubova, I., Khvotchev, M., Liu, S., Huryeva, I., Südhof, T. C., Rizo, J. (2007) Munc18-1 binds directly to the neuronal SNARE complex. Proc Natl Acad Sci U S A. 104:2697-2702.

Fischer von Mollard, G., Südhof, T. C., Jahn, R. (1991) A small GTP-binding protein dissociates from synaptic vesicles during exocytosis. Nature. 349:79-81.

Fisher, R. J., Pevsner J., and Burgoyne, R. D. (2001) Control of fusion pore dynamics during exocytosis by Munc18. Science. 291:875-878.

Fujita, Y., Sasaki, T., Fukui, K., Kotani, H., Kimura, T., Hata, Y., Südhof, T. C., Scheller, R. H., Takai, Y. (1996) Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin. J Biol Chem. 271:7265-7268.

Geppert, M., Südhof, T. C. (1998) RAB3 and synaptotagmin: The yin and yang of synaptic membrane fusion. Annu Rev Neurosci. 21:75-95.

Gladycheva, S. E., Ho, C. S., Lee, Y. Y., Stuenkel, E. L. (2004) Regulation of syntaxin1A-munc18 complex for SNARE pairing in HEK293 cells. J Physiol. 558:857-871.

Graham, M. E., Handley, M. T., Barclay, J. W., Ciufo, L. F., Barrow, S. L., Morgan, A., Burgoyne, R. D. (2008) A gain-of-function mutant of Munc18-1 stimulates secretory granule recruitment and exocytosis and reveals a direct interaction of Munc18-1 with Rab3. Biochem J. 409:407-416.

Grasso, A., Alemà, S., Rufini, S., Senni, M. I. (1980) Black widow spider toxin-induced calcium fluxes and transmitter release in a neurosecretory cell line. Nature. 283:774-776.

Guan, R., Dai, H., Rizo, J. (2008) Binding of the Munc13-1 MUN domain to membrane-anchored SNARE complexes. Biochemistry. 47:1471-1481.

Gulyás-Kovács, A., de Wit, H., Milosevic, I., Kochubey, O., Toonen, R., Klingauf, J., Verhage, M., Sørensen, J. B. (2007) Munc18-1: sequential interactions with the fusion machinery stimulate vesicle docking and priming. J Neurosci. 27:8676-8686.

Holroyd, P., Lang, T., Wenzel, D., De Camilli, P., Jahn, R. (2002) Imaging direct, dynamin-dependent recapture of fusing secretory granules on plasma membrane lawns from PC12 cells. Proc Natl Acad Sci USA. 99:16806-16811.

Holz, R. W., Bittner, M. A., Senter, R. A. (1992) Regulated exocytotic fusion I: Chromaffin cells and PC12 cells. Methods Enzymol. 219:165-178.

Holz, R. W., Brondyk, W. H., Senter, R. A., Kuizon, L.,Macara, I. G. (1994) Evidence for the involvement of Rab3A in Ca2+-dependent exocytosis from adrenal chromaffin cells. J Biol Chem. 269:10229-10234.

Johannes, L., Lledo, P. M., Roa, M., Vincent, J. D., Henry, J. P., Darchen, F. (1994) The GTPase Rab3a negatively controls calcium-dependent exocytosis in neuroendocrine cells. EMBO J. 13:2029-2037.

Jahn, R., Lang, T., Südhof, T. C. (2003) Membrane fusion. Cell. 112:519-533.

Jahn, R., Scheller, R. H. (2006) SNAREs-engines for membrane fusion. Nat Rev Mol Cell Biol. 7:631-643.

Koushika, S. P., Richmond, J. E., Hadwiger, G., Weimer, R. M., Jorgensen, E. M., Nonet, M. L. (2001) A post-docking role for active zone protein Rim. Nat Neurosci. 4:997-1005.

Lang, T., Wacker, I., Steyer, J., Kaether, C., Wunderlich, I., Soldati, T., Gerdes, H. H., Almers, W. (1997) Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy. Neuron. 18:857-863.

Leenders, A. G., Lopes da Silva, F. H., Ghijsen, W.E., Verhage, M. (2001) Rab3a is involved in transport of synaptic vesicles to the active zone in mouse brain nerve terminals. Mol. Biol. Cell. 12:3095-3102.

Lin, C. C., Huang, C. C., Lin, K. H., Cheng, K. H., Yang, D. M., Tsai, Y. S., Ong, R. Y., Huang, Y. N., Kao LS. (2007) Visualization of Rab3A dissociation during exocytosis: a study by total internal reflection microscopy. J Cell Physiol. 211:316-326.

Liu, J., Ernst, S. A., Gladycheva, S. E., Lee, Y.Y., Lentz, S.I., Ho, C.S., Li, Q., Stuenkel, E. L. (2004) Fluorescence resonance energy transfer reports properties of syntaxin1A interaction with Munc18-1 in Vivo. J Biol Chem. 279:55924-55936.

Lu, J., Machius, M., Dulubova, I., Dai, H., Südhof, T. C., Tomchick, D. R., Rizo, J. (2006) Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch. PLoS Biol. 4:e192.

Macara, I. G. (1994) Role of the Rab3A GTPase in regulated secretion from neuroendocrine cells. Trends Endocrinol Metab. 5:267-271.

Maruyama, I. N., Brenner, S. (1991) A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene of Caenorhabditis elegans. Proc Natl Acad Sci USA. 88:5729-5733.

Matteoli, M., Takei, K., Cameron, R., Hurlbut, P., Johnston, P. A., Südhof, T. C., Jahn, R., De Camilli, P. (1991) Association of Rab3A with synaptic vesicles at late stages of the secretory pathway. J Cell Biol. 115:625-633.

Medine, C. N., Rickman, C., Chamberlain, L. H., Duncan, R. R. (2007) Munc18-1 prevents the formation of ectopic SNARE complexes in living cells. J Cell Sci. 120:4407-4415.

Ohya, T., Sasaki, T., Kato, M., Takai, Y. (1998) Involvement of Rabphilin3 in endocytosis through interaction with Rabaptin5. J Biol Chem. 273:613-617.

Park, J. B., Farnsworth, C. C., Glomset, J. A. (1997) Ca2+/calmodulin causes Rab3A to dissociate from synaptic membranes. J Biol Chem. 272:20857-20865.

Patterson, G. H., Knobel, S. M., Sharif, W. D., Kain, S. R., Piston, D. W. (1997) Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Biophys J. 73:2782-2790.

Perrais, D., Kleppe, I. C., Taraska, J. W., Almers, W. (2004) Recapture after exocytosis causes differential retention of protein in granules of bovine chromaffin cells. J Physiol. 560:413-428.

Pevsner, J., Hsu, S. C., Scheller, R. H. (1994) n-Sec1: a neural-specific syntaxin -binding protein. Proc Natl Acad Sci USA. 91:1445-1449.
Rhee, J. S., Betz, A., Pyott, S., Reim, K., Varoqueaux, F., Augustin, I., Hesse, D., Südhof, T. C., Takahashi, M., Rosenmund, C., Brose, N. (2002) ??phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell. 108:121-133.

Sakisaka, T., Meerlo, T., Matteson, J., Plutner, H., Balch, W. E. (2002) Rab-alphaGDI activity is regulated by a Hsp90 chaperone complex. EMBO J. 21:6125-6135.

Schlüter, O. M., Khvotchev, M., Jahn, R., Südhof, T. C. (2002) Localization versus function of Rab3 proteins. Evidence for a common regulatory role in controlling fusion. J Biol Chem. 277:40919-40929.

Schneggenburger, R., Neher, E. (2005) Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol. 15:266-274.

Schoch, S., Castillo, P. E., Jo, T., Mukherjee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R. C., Südhof, T. C. (2002) RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature. 415:321-326.

Sheng, Z. H., Rettig, J., Takahashi, M., Catterall, W. A. (1994) Identification of a syntaxin-binding site on N-type calcium channels. Neuron. 13:1303-1313.

Slembrouck, D., Annaert, W. G., Wang, J. M., Potter, W. P. (1999) Rab3 is present on endosomes from bovine chromaffin cells in primary culture. J Cell Sci. 112:641-649.


Söllner, T., Bennett, M. K., Whiteheart, S. W., Scheller, R. H., 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.

Stahl, B., von Mollard, G. F., Walch-Solimena, C., Jahn, R. (1994) GTP cleavage by the small GTP-binding protein Rab3A is associated with exocytosis of synaptic vesicles induced by alpha-latrotoxin. J Biol Chem. 269:24770-24776.

Stanley, E. F. (1993) Single calcium channels and acetylcholine release at a presynaptic nerve terminal. Neuron. 11:1007-1011.

Staunton, J., Ganetzky, B., Nonet, M. L. (2001) Rabphilin potentiates soluble N-ethylmaleimide sensitive factor attachment protein receptor function independently of rab3. J Neurosci. 21:9255-9264.

Stevens, D. R., Wu, Z. X., Matti, U., Junge, H. J., Schirra, C., Becherer, U., Wojcik, S. M., Brose, N., Rettig, J. (2005) Identification of the minimal protein domain required for priming activity of Munc13-1. Curr Biol. 15:2243-2248.

Steyer, J. A., Horstmann, H., Almers, W. (1997) Transport, docking and exocytosis of single secretory granules in live chromaffin cells. Nature. 388:474-478.

Südhof, T. C., and Rothman, J. E. (2009) Membrane fusion: grappling with SNARE and SM proteins. Science. 323:474-477.

Südhof, T. C. (2004) The synaptic vesicle cycle. Annu Rev Neurosci. 27:509-547.
Taraska, J.W., Perrais, D., Ohara-Imaizumi, M., Nagamatsu, S., Almers, W. (2003) Secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells. Proc Natl Acad Sci USA. 100:2070-2075.

Tsuboi, T., McMahon, H. T., Rutter, G. A. (2004) Mechanisms of dense core vesicle recapture following “kiss and run” (“cavicapture”) exocytosis in insulin-secreting cells. J Biol Chem. 279:47115-47124.

Tsuboi, T., and Fukuda, M. (2006) Rab3A and Rab27A cooperatively regulate the docking step of dense-core vesicle exocytosis in PC12 cells. J Cell Sci. 119:2196-2203.

van Weering, J. R., Toonen, R. F., Verhage, M. (2007) The role of Rab3a in secretory vesicle docking requires association/dissociation of guanidine phosphates and Munc18-1. PLoS One. 2:e616.

Virmani, T., Ertunc, M., Sara, Y., Mozhayeva, M., Kavalali, E. T. (2005) Phorbol esters target the activity-dependent recycling pool and spare spontaneous vesicle recycling. J Neurosci. 25:10922-10929.

Voets, T., Toonen, R. F., Brian, E. C., de Wit, H., Moser, T., Rettig, J., Südhof, T. C., Neher, E., Verhage, M. (2001) Munc18-1 promotes large dense-core vesicle docking. Neuron. 31:581-591.

Verhage, M., Maia, A. S., Plomp, J. J., Brussaard, A. B., Heeroma, J. H., Vermeer, H., Toonen, R. F., Hammer, R. E., van den Berg, T. K., Missler, M., Geuze, H. J., Südhof, T. C. (2000) Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science. 287:864-869.

Wang, C. T., Lu, J. C., Bai, J., Chang, P. Y., Martin, T. F., Chapman, E. R., Jackson, M. B. (2003) Different domains of synaptotagmin control the choice between kiss-and-run and full fusion. Nature. 424:943-947.

Wang, X., Thiagarajan, R., Wang, Q., Tewolde, T., Rich, M. M., Engisch, K. L. (2008) Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism. J Physiol. 586:3949-3962.

Wang, Y., Okamoto, M., Schmitz, F., Hofmann, K., Südhof, T. C. (1997) Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Nature. 388:593-598

Weninger, K., Bowen, M. E., Choi, U. B., Chu, S., Brunger, A. T. (2008) Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex. Structure. 16:308-320.

Wierda, K. D., Toonen, R.F., de Wit, H., Brussaard, A. B., Verhage, M. (2007) Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron. 54:275-290.

Yang, B., Steegmaier, M., Gonzalez, L. C. Jr., Scheller, R. H. (2000) nSec1 binds a closed conformation of syntaxin1A. J Cell Biol. 148:247-252.


Yang, D. M., Huang, C. C., Lin, H. Y., Tsai, D. P., Kao, L. S., Chi, C. W., Lin, C. C. (2003) Tracking of secretory vesicles of PC12 cells by total internal reflection fluorescence microscopy. J Microsc. 209:223-227.

Zenisek, D., Steyer, J. A., Almers, W. (2000) Transport, capture and exocytosis of single synaptic vesicles at active zones. Nature. 406:849-854.

Zenisek, D., Steyer, J. A., Feldman, M. E., Almers, W. A. (2002) Membrane marker leaves synaptic vesicles in milliseconds after exocytosis in retinal bipolar cells. Neuron. 35:1085-1097.

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