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

• DOI: 10.1016/j.celrep.2018.10.033
• Publication Date: 2018-11-06T16:54:17Z
• Authors: Shehrazade Dahimene; Karen M. Page; Ivan Kadurin; Laurent Ferron; Dominique Y. Ho; Gareth T. Powell; Wendy S. Pratt; Stephen W. Wilson; Annette C. Dolphin
• Keywords: Immunoprecipitation; Cav1.2

Voltage-gated calcium channel auxiliary α2δ subunits are important for trafficking and function. Here, we compare the effects of α2δ-1 an α2δ-like protein called Cachd1 on neuronal N-type (CaV2.2) channels, which in neurotransmission. Previous structural studies show VWA domain interacting with first loop CaV1.1 domain-I via its metal ion-dependent adhesion site (MIDAS) motif additional Cache interactions. has a disrupted MIDAS motif. However, increases CaV2.2 currents substantially (although less than α2δ-1) cell surface expression by reducing endocytosis. Although abolished mutation Asp122 domain-I, mediates interaction domain, responses unaffected. Furthermore, co-immunoprecipitates inhibits co-immunoprecipitation CaV2.2. also competes trafficking. Thus, influences both function can inhibit to α2δ-1.