PRRT2 modulates presynaptic Ca²⁺ influx by interacting with P/Q-type channels.

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-ty

SUBMITTER: Ferrante D 

PROVIDER: S-EPMC8220258 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature