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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.

Authors :
Ferrante D
Sterlini B
Prestigio C
Marte A
Corradi A
Onofri F
Tortarolo G
Vicidomini G
Petretto A
MuiĆ  J
Thalhammer A
Valente P
Cingolani LA
Benfenati F
Baldelli P
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.)

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