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CAST/ELKS Proteins Control Voltage-Gated Ca 2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse.

Authors :
Dong W
Radulovic T
Goral RO
Thomas C
Suarez Montesinos M
Guerrero-Given D
Hagiwara A
Putzke T
Hida Y
Abe M
Sakimura K
Kamasawa N
Ohtsuka T
Young SM Jr
Source :
Cell reports [Cell Rep] 2018 Jul 10; Vol. 24 (2), pp. 284-293.e6.
Publication Year :
2018

Abstract

In the presynaptic terminal, the magnitude and location of Ca <superscript>2+</superscript> entry through voltage-gated Ca <superscript>2+</superscript> channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein family at the calyx of Held, a Ca <subscript>V</subscript> 2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the Ca <subscript>V</subscript> 2.1 current density with concomitant reductions in Ca <subscript>V</subscript> 2.1 channel numbers and clusters. Surprisingly, deletion of CAST/ELKS increases release probability while decreasing the readily releasable pool, with no change in active zone ultrastructure. In addition, Ca <superscript>2+</superscript> channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of Ca <subscript>V</subscript> 2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity.<br /> (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2211-1247
Volume :
24
Issue :
2
Database :
MEDLINE
Journal :
Cell reports
Publication Type :
Academic Journal
Accession number :
29996090
Full Text :
https://doi.org/10.1016/j.celrep.2018.06.024