Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2010 Aug 11;5(8):e12018. doi: 10.1371/journal.pone.0012018.

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

Author information

  • 1Zentrum für Molekulare Neurobiologie, University of Hamburg, Hamburg, Germany.

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.

PMID:
20711454
[PubMed - indexed for MEDLINE]
PMCID:
PMC2920317
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk