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Cryo-electron tomography reveals a critical role of RIM1? in synaptic vesicle tethering.


ABSTRACT: Synaptic vesicles are embedded in a complex filamentous network at the presynaptic terminal. Before fusion, vesicles are linked to the active zone (AZ) by short filaments (tethers). The identity of the molecules that form and regulate tethers remains unknown, but Rab3-interacting molecule (RIM) is a prominent candidate, given its central role in AZ organization. In this paper, we analyzed presynaptic architecture of RIM1? knockout (KO) mice by cryo-electron tomography. In stark contrast to previous work on dehydrated, chemically fixed samples, our data show significant alterations in vesicle distribution and AZ tethering that could provide a structural basis for the functional deficits of RIM1? KO synapses. Proteasome inhibition reversed these structural defects, suggesting a functional recovery confirmed by electrophysiological recordings. Altogether, our results not only point to the ubiquitin-proteasome system as an important regulator of presynaptic architecture and function but also show that the tethering machinery plays a critical role in exocytosis, converging into a structural model of synaptic vesicle priming by RIM1?.

SUBMITTER: Fernandez-Busnadiego R 

PROVIDER: S-EPMC3664715 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Cryo-electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering.

Fernández-Busnadiego Rubén R   Asano Shoh S   Oprisoreanu Ana-Maria AM   Sakata Eri E   Doengi Michael M   Kochovski Zdravko Z   Zürner Magdalena M   Stein Valentin V   Schoch Susanne S   Baumeister Wolfgang W   Lucić Vladan V  

The Journal of cell biology 20130501 5


Synaptic vesicles are embedded in a complex filamentous network at the presynaptic terminal. Before fusion, vesicles are linked to the active zone (AZ) by short filaments (tethers). The identity of the molecules that form and regulate tethers remains unknown, but Rab3-interacting molecule (RIM) is a prominent candidate, given its central role in AZ organization. In this paper, we analyzed presynaptic architecture of RIM1α knockout (KO) mice by cryo-electron tomography. In stark contrast to previ  ...[more]

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