Molecular basis of the PIP₂-dependent regulation of Ca_V2.2 channel and its modulation by Ca_V β subunits.

ABSTRACT: High-voltage-activated Ca²⁺ (Ca_V) channels that adjust Ca²⁺ influx upon membrane depolarization are differentially regulated by phosphatidylinositol 4,5-bisphosphate (PIP₂) in an auxiliary Ca_V β subunit-dependent manner. However, the molecular mechanism by which the β subunits control the PIP₂ sensitivity of Ca_V channels remains unclear. By engineering various α1B and β constructs in tsA-201 cells, we reported that at least two PIP₂-binding sites, including the polybasic residues at the C-terminal end of I-II loop and the binding pocket in S4_II domain, exist in the Ca_V2.2 channels. Moreover, they were distinctly engaged in the regulation of channel gating depending on the coupled C

SUBMITTER: Park CG 

PROVIDER: S-EPMC9662827 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature