Engineering selectivity into RGK GTPase inhibition of voltage-dependent calcium channels.

ABSTRACT: Genetically encoded inhibitors for voltage-dependent Ca²⁺ (Ca_V) channels (GECCIs) are useful research tools and potential therapeutics. Rad/Rem/Rem2/Gem (RGK) proteins are Ras-like G proteins that potently inhibit high voltage-activated (HVA) Ca²⁺ (Ca_V1/Ca_V2 family) channels, but their nonselectivity limits their potential applications. We hypothesized that nonselectivity of RGK inhibition derives from their binding to auxiliary Ca_Vβ-subunits. To investigate latent Ca_Vβ-independent components of inhibition, we coexpressed each RGK individually with Ca_V1 (Ca_V1.2/Ca_V1.3) or Ca_V2 (Ca_V2.1/Ca_V2.2) channels reconstituted in HEK293 cells with either wild-t

SUBMITTER: Puckerin AA 

PROVIDER: S-EPMC6255209 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature