Synaptotagmin-1 Docks Secretory Vesicles to Syntaxin-1/SNAP-25 Acceptor Complexes

被引：213

作者：

de Wit, Heidi ^{[3
,4
]}

Walter, Alexander M. ^{[1
]}

Milosevic, Ira ^{[1
]}

Gulyas-Kovacs, Attila ^{[1
]}

Riedel, Dietmar ^{[2
]}

Sorensen, Jakob B. ^{[1
,5
]}

Verhage, Matthijs ^{[3
,4
]}

机构：

[1] Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany

[2] Max Planck Inst Biophys Chem, Electron Microscopy Lab, D-37077 Gottingen, Germany

[3] Vrije Univ Amsterdam, Dept Funct Genom, Ctr Neurogenom & Cognit Res, NL-1081 HV Amsterdam, Netherlands

[4] VU Med Ctr, NL-1081 HV Amsterdam, Netherlands

[5] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark

来源：

CELL | 2009年 / 138卷 / 05期

关键词：

MEMBRANE-FUSION; SNARE COMPLEX; T-SNARE; NEUROTRANSMITTER RELEASE; CONFORMATIONAL SWITCH; REGULATED EXOCYTOSIS; SYNAPTIC VESICLES; CHROMAFFIN CELLS; PLASMA-MEMBRANE; C2B DOMAIN;

D O I：

10.1016/j.cell.2009.07.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Docking, the initial association of secretory vesicles with the plasma membrane, precedes formation of the SNARE complex, which drives membrane fusion. For many years, the molecular identity of the docked state, and especially the vesicular docking protein, has been unknown, as has the link to SNARE complex assembly. Here, using adrenal chromaffin cells, we identify the vesicular docking partner as synaptotagmin-1, the calcium sensor for exocytosis, and SNAP-25 as an essential plasma membrane docking factor, which, together with the previously known docking factors Munc18-1 and syntaxin, form the minimal docking machinery. Moreover, we show that the requirement for Munc18-1 in docking, but not fusion, can be overcome by stabilizing syntaxin/SNAP-25 acceptor complexes. These findings, together with cross-rescue, double-knockout, and electrophysiological data, lead us to propose that vesicles dock when synaptotagmin-1 binds to syntaxin/SNAP-25 acceptor complexes, whereas Munc18-1 is required for the downstream association of synaptobrevin to form fusogenic SNARE complexes.

引用

页码：935 / 946

页数：12

共 58 条

[51] Munc18-1 promotes large dense-core vesicle docking [J].

Voets, T ;

Toonen, RF ;

Brian, EC ;

de Wit, H ;

Moser, T ;

Rettig, J ;

Südhof, TC ;

Neher, E ;

Verhage, M .

NEURON, 2001, 31 (04) :581-591

[52]

Weimer RM, 2005, CURR TOP DEV BIOL, V65, P83

[53] Defects in synaptic vesicle docking in unc-18 mutants [J].

Weimer, RM ;

Richmond, JE ;

Davis, WS ;

Hadwiger, G ;

Nonet, ML ;

Jorgensen, EM .

NATURE NEUROSCIENCE, 2003, 6 (10) :1023-1030

[54] Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex [J].

Weninger, Keith ;

Bowen, Mark E. ;

Choi, Ucheor B. ;

Chu, Steven ;

Brunger, Axel T. .

STRUCTURE, 2008, 16 (02) :308-320

[55] The neuronal t-SNARE complex is a parallel four-helix bundle [J].

Xiao, WZ ;

Poirier, MA ;

Bennett, MK ;

Shin, YK .

NATURE STRUCTURAL BIOLOGY, 2001, 8 (04) :308-311

[56] The Janus-faced nature of the C2B domain is fundamental for synaptotagmin-1 function [J].

Xue, Mingshan ;

Ma, Cong ;

Craig, Timothy K. ;

Rosenmund, Christian ;

Rizo, Josep .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2008, 15 (11) :1160-1168

[57] Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis [J].

Zhang, XD ;

Kim-Miller, MJ ;

Fukuda, M ;

Kowalchyk, JA ;

Martin, TFJ .

NEURON, 2002, 34 (04) :599-611

[58] Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes [J].

Zilly, Felipe E. ;

Sorensen, Jakob B. ;

Jahn, Reinhard ;

Lang, Thorsten .

PLOS BIOLOGY, 2006, 4 (10) :1789-1797

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