PRRT2 modulates presynaptic Ca2+ influx by interacting with P/Q-type channels.
Cell Rep
; 35(11): 109248, 2021 06 15.
Article
em En
| MEDLINE
| ID: mdl-34133925
ABSTRACT
Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca2+ 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 Ca2+ and associated with a reduced contribution of P/Q-type Ca2+ channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca2+ 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 Ca2+ channels. At presynaptic terminals lacking PRRT2, P/Q-type Ca2+ channels reduce their clustering at the active zone, with a corresponding decrease in the P/Q-dependent presynaptic Ca2+ signal. The data highlight the central role of PRRT2 in ensuring the physiological Ca2+ sensitivity of the release machinery at glutamatergic synapses.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
/
Cálcio
/
Terminações Pré-Sinápticas
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Proteínas de Membrana
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália