Synaptotagmin-1 may be a distance regulator acting upstream of SNARE nucleation

被引：102

作者：

van den Bogaart, Geert ^{[1
]}

Thutupalli, Shashi ^{[2
]}

Risselada, Jelger H. ^{[3
]}

Meyenberg, Karsten ^{[4
]}

Holt, Matthew ^{[1
]}

Riedel, Dietmar ^{[5
]}

Diederichsen, Ulf ^{[4
]}

Herminghaus, Stephan ^{[2
]}

Grubmueller, Helmut ^{[3
]}

Jahn, Reinhard ^{[1
]}

机构：

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

[2] Max Planck Inst Dynam & Self Org, Dept Dynam Complex Fluids, Gottingen, Germany

[3] Max Planck Inst Biophys Chem, Dept Theoret & Computat Biophys, D-37077 Gottingen, Germany

[4] Univ Gottingen, Inst Organ & Biomol Chem, Gottingen, Germany

[5] Max Planck Inst Biophys Chem, Facil Electron Microscopy, D-37077 Gottingen, Germany

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 07期

基金：

美国国家卫生研究院;

关键词：

MEMBRANE-FUSION; NEUROTRANSMITTER RELEASE; VESICLE FUSION; C2B DOMAIN; T-SNARE; LATERAL MOBILITY; PLASMA-MEMBRANE; SINGLE-MOLECULE; FORCE-FIELD; COMPLEX;

D O I：

10.1038/nsmb.2061

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：

Synaptotagmin-1 triggers Ca2+-sensitive, rapid neurotransmitter release by promoting interactions between SNARE proteins on synaptic vesicles and the plasma membrane. How synaptotagmin-1 promotes this interaction is unclear, and the massive increase in membrane fusion efficiency of Ca2+-bound synaptotagmin-1 has not been reproduced in vitro. However, previous experiments have been performed at relatively high salt concentrations, screening potentially important electrostatic interactions. Using functional reconstitution in liposomes, we show here that at low ionic strength SNARE-mediated membrane fusion becomes strictly dependent on both Ca2+ and synaptotagmin-1. Under these conditions, synaptotagmin-1 functions as a distance regulator that tethers the liposomes too far from the plasma membrane for SNARE nucleation in the absence of Ca2+, but while bringing the liposomes close enough for membrane fusion in the presence of Ca2+. These results may explain how the relatively weak electrostatic interactions between synaptotagmin-1 and membranes substantially accelerate fusion.

引用

页码：805 / U82

页数：9