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PMID: 20711454 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

CHL1 is a selective organizer of the presynaptic machinery chaperoning the SNARE complex.

PloS one ·Vol. 5 ·No. 8 ·2010-08-11 ·Pages e12018

Andreyeva A, Leshchyns'ka I, Knepper M, Betzel C, Redecke L, Sytnyk V, Schachner M

Abstract

Proteins constituting the presynaptic machinery of vesicle release undergo substantial conformational changes during the process of exocytosis. While changes in the conformation make proteins vulnerable to aggregation and degradation, little is known about synaptic chaperones which counteract these processes. We show that the cell adhesion molecule CHL1 directly interacts with and regulates the activity of the synaptic chaperones Hsc70, CSP and alphaSGT. CHL1, Hsc70, CSP and alphaSGT form predominantly CHL1/Hsc70/alphaSGT and CHL1/CSP complexes in synapses. Among the various complexes formed by CHL1, Hsc70, CSP and alphaSGT, SNAP25 and VAMP2 induce chaperone activity only in CHL1/Hsc70/alphaSGT and CHL1/CSP complexes, respectively, indicating a remarkable selectivity of a presynaptic chaperone activity for proteins of the exocytotic machinery. In mice with genetic ablation of CHL1, chaperone activity in synapses is reduced and the machinery for synaptic vesicle exocytosis and, in particular, the SNARE complex is unable to sustain prolonged synaptic activity. Thus, we reveal a novel role for a cell adhesion molecule in selective activation of the presynaptic chaperone machinery.

MeSH Terms
Animals Brain/cytology,metabolism,physiology Carrier Proteins/metabolism Cell Adhesion Molecules/metabolism HSC70 Heat-Shock Proteins/metabolism HSP40 Heat-Shock Proteins/metabolism Membrane Proteins/metabolism Mice Molecular Chaperones/metabolism Protein Binding SNARE Proteins/metabolism Stress, Physiological Substrate Specificity Synapses/metabolism Synaptic Vesicles/metabolism Synaptosomal-Associated Protein 25/metabolism Time Factors Vesicle-Associated Membrane Protein 2/metabolism
Chemicals
Carrier Proteins Cell Adhesion Molecules Chl1 protein, mouse HSC70 Heat-Shock Proteins HSP40 Heat-Shock Proteins Membrane Proteins Molecular Chaperones SNARE Proteins Synaptosomal-Associated Protein 25 Vesicle-Associated Membrane Protein 2 cysteine string protein vesicle-associated membrane protein 2, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Andreyeva Aksana
Zentrum für Molekulare Neurobiologie, University of Hamburg, Hamburg, Germany.
Leshchyns'ka Iryna
Knepper Michael
Betzel Christian
Redecke Lars
Sytnyk Vladimir
Schachner Melitta
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0012018
Published
2010-08-11
Epub
2010-00-11
Pages
e12018
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2920317
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0012018 PMC Full Text View journal details
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