RIM-Binding Protein, a Central Part of the Active Zone, Is Essential for Neurotransmitter Release

被引：215

作者：

Liu, Karen S. Y. ^{[2
]}

Siebert, Matthias ^{[1
]}

Mertel, Sara ^{[2
]}

Knoche, Elena ^{[1
]}

Wegener, Stephanie ^{[1
]}

Wichmann, Carolin ^{[1
]}

Matkovic, Tanja ^{[2
]}

Muhammad, Karzan ^{[2
]}

Depner, Harald ^{[2
]}

Mettke, Christoph ^{[2
]}

Bueckers, Johanna ^{[3
]}

Hell, Stefan W. ^{[3
]}

Mueller, Martin ^{[4
]}

Davis, Graeme W. ^{[4
]}

Schmitz, Dietmar ^{[1
,5
]}

Sigrist, Stephan J. ^{[1
,2
]}

机构：

[1] Charite, NeuroCure Cluster Excellence, D-10117 Berlin, Germany

[2] Free Univ Berlin, Inst Biol, Dept Genet, D-14195 Berlin, Germany

[3] Max Planck Inst Biophys Chem, Dept Nanobiophoton, D-37077 Gottingen, Germany

[4] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[5] DZNE German Ctr Neurodegenerat Dis, D-10117 Berlin, Germany

来源：

SCIENCE | 2011年 / 334卷 / 6062期

基金：

瑞士国家科学基金会;

关键词：

SYNAPTIC CALCIUM-CHANNEL; CA2+ CHANNELS; DROSOPHILA; BRUCHPILOT; MATURATION; MOLECULES; CACOPHONY; FAMILY;

D O I：

10.1126/science.1212991

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)-binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca(2+) channel field. In drbp mutants, Ca(2+) channel clustering and Ca(2+) influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca(2+) channels, and the SV fusion machinery.

引用

页码：1565 / 1569

页数：5

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