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PRRT2 modulates presynaptic Ca 2+ influx by interacting with P/Q-type channels.
PRRT2 modulates presynaptic Ca 2+ influx by interacting with P/Q-type channels.
- Source :
-
Cell reports [Cell Rep] 2021 Jun 15; Vol. 35 (11), pp. 109248. - Publication Year :
- 2021
-
Abstract
- Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca <superscript>2+</superscript> dependence of glutamatergic transmission. We find that either acute or constitutive PRRT2 deletion induces a significant decrease in the amplitude of evoked excitatory postsynaptic currents (eEPSCs) that is insensitive to extracellular Ca <superscript>2+</superscript> and associated with a reduced contribution of P/Q-type Ca <superscript>2+</superscript> channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca <superscript>2+</superscript> currents due to a decreased membrane targeting of the channel with unchanged total expression levels. Co-immunoprecipitation, pull-down assays, and proteomics reveal a specific and direct interaction of PRRT2 with P/Q-type Ca <superscript>2+</superscript> channels. At presynaptic terminals lacking PRRT2, P/Q-type Ca <superscript>2+</superscript> channels reduce their clustering at the active zone, with a corresponding decrease in the P/Q-dependent presynaptic Ca <superscript>2+</superscript> signal. The data highlight the central role of PRRT2 in ensuring the physiological Ca <superscript>2+</superscript> sensitivity of the release machinery at glutamatergic synapses.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Cell Membrane metabolism
Excitatory Postsynaptic Potentials
Extracellular Space chemistry
Glutamates metabolism
HEK293 Cells
Humans
Membrane Proteins chemistry
Membrane Proteins deficiency
Mice, Inbred C57BL
Mice, Knockout
Neurons metabolism
Protein Binding
Synaptic Transmission
Mice
Calcium metabolism
Calcium Channels metabolism
Membrane Proteins metabolism
Presynaptic Terminals metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 35
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34133925
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109248