The α₂δ-like Protein Cachd1 Increases N-type Calcium Currents and Cell Surface Expression and Competes with α₂δ-1.

ABSTRACT: Voltage-gated calcium channel auxiliary α2δ subunits are important for channel trafficking and function. Here, we compare the effects of α2δ-1 and an α2δ-like protein called Cachd1 on neuronal N-type (Ca_V2.2) channels, which are important in neurotransmission. Previous structural studies show the α2δ-1 VWA domain interacting with the first loop in Ca_V1.1 domain-I via its metal ion-dependent adhesion site (MIDAS) motif and additional Cache domain interactions. Cachd1 has a disrupted MIDAS motif. However, Cachd1 increases Ca_V2.2 currents substantially (although less than α2δ-1) and increases Ca_V2.2 cell surface expression by reducing endocytosis. Although the effects of α2δ-1 are abolished by mutation of Asp122 in Ca_V2.2 domain-I, which

SUBMITTER: Dahimene S 

PROVIDER: S-EPMC6231325 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature