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

Fernandez-Busnadiego, R., Asano, S., Oprisoreanu, A.-M., Sakata, E., Doengi, M., Kochovski, Z., et al. (2013). Cryo-electron tomography reveals a critical role of RIM1 alpha in synaptic vesicle tethering. JOURNAL OF CELL BIOLOGY, 201(5), 725-740. doi:10.1083/jcb.201206063.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-F661-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-F662-5
Genre: Journal Article

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 Creators:
Fernandez-Busnadiego, Ruben1, Author              
Asano, Shoh1, Author              
Oprisoreanu, Ana-Maria2, Author
Sakata, Eri1, Author              
Doengi, Michael2, Author
Kochovski, Zdravko1, Author              
Zuemer, Magdalena2, Author
Stein, Valentin2, Author              
Schoch, Susanne2, Author
Baumeister, Wolfgang1, Author              
Lucic, Vladan1, Author              
Affiliations:
1Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              
2external, ou_persistent22              

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Free keywords: PRESYNAPTIC ACTIVE ZONE; UBIQUITIN-PROTEASOME SYSTEM; PERCOLL GRADIENT PROCEDURE; NEUROTRANSMITTER RELEASE; PROTEIN RIM1-ALPHA; RIM PROTEINS; MOLECULAR-ORGANIZATION; SUBCELLULAR-FRACTIONS; GLUTAMATE RELEASE; NERVE-TERMINALS
 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..

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Language(s): eng - English
 Dates: 2013-05-27
 Publication Status: Published in print
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: ISI: 000319504500010
DOI: 10.1083/jcb.201206063
 Degree: -

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Title: JOURNAL OF CELL BIOLOGY
Source Genre: Journal
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Publ. Info: 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA : ROCKEFELLER UNIV PRESS
Pages: - Volume / Issue: 201 (5) Sequence Number: - Start / End Page: 725 - 740 Identifier: ISSN: 0021-9525