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CAST/ELKS Proteins Control Voltage-Gated Ca 2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse.
- 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.)
- Subjects :
- Action Potentials physiology
Animals
Cytoskeletal Proteins deficiency
Kinetics
Mice, Inbred C57BL
Nerve Tissue Proteins deficiency
Neurotransmitter Agents metabolism
Probability
Synapses ultrastructure
Synaptic Transmission physiology
rab GTP-Binding Proteins
Calcium Channels, N-Type metabolism
Carrier Proteins metabolism
Cytoskeletal Proteins metabolism
Ion Channel Gating
Nerve Tissue Proteins metabolism
Synapses metabolism
Subjects
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