Dominant-negative suppression of Cav2.1 currents by alpha(1)2.1 truncations requires the conserved interaction domain for beta subunits.

ABSTRACT: Episodic ataxia type 2 (EA2) is an autosomal dominant disorder arising from CACNA1A mutations, which commonly predict heterozygous expression of Ca(v)2.1 calcium channels with truncated alpha(1)2.1 pore subunits. We hypothesized that alpha(1)2.1 truncations in EA2 exert dominant-negative effects on the function of wild-type subunits. Wild-type and truncated alpha(1)2.1 subunits with fluorescent protein tags were transiently co-expressed in cells stably expressing Ca(v) auxiliary beta subunits, which facilitate alpha1 subunit functional expression through high-affinity interactions with the alpha interaction domain (AID). Co-expression of wild-type subunits with truncations often resulted in severely reduced whole-cell currents compared to expression of wild-type subunits alone. Cellular im

SUBMITTER: Raike RS 

PROVIDER: S-EPMC3236250 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature