CHL1 is a selective organizer of the presynaptic machinery chaperoning the SNARE complex.
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CHL1 is a selective organizer of the presynaptic machinery chaperoning the SNARE complex. / Andreyeva, Aksana; Leshchyns´ka, Iryna; Knepper, Michael; Betzel, Christian; Redecke, Lars; Sytnyk, Vladimir; Schachner, Melitta.
in: PLOS ONE, Jahrgang 5, Nr. 8, 8, 2010, S. 12018.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - CHL1 is a selective organizer of the presynaptic machinery chaperoning the SNARE complex.
AU - Andreyeva, Aksana
AU - Leshchyns´ka, Iryna
AU - Knepper, Michael
AU - Betzel, Christian
AU - Redecke, Lars
AU - Sytnyk, Vladimir
AU - Schachner, Melitta
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0012018
DO - 10.1371/journal.pone.0012018
M3 - SCORING: Zeitschriftenaufsatz
VL - 5
SP - 12018
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 8
M1 - 8
ER -
