Ca_V channels reject signaling from a second CaM in eliciting Ca²⁺-dependent feedback regulation.

ABSTRACT: Calmodulin (CaM) regulation of voltage-gated calcium (Ca_V1-2) channels is a powerful Ca²⁺-feedback mechanism to adjust channel activity in response to Ca²⁺ influx. Despite progress in resolving mechanisms of CaM-Ca_V feedback, the stoichiometry of CaM interaction with Ca_V channels remains ambiguous. Functional studies that tethered CaM to Ca_V1.2 suggested that a single CaM sufficed for Ca²⁺ feedback, yet biochemical, FRET, and structural studies showed that multiple CaM molecules interact with distinct interfaces within channel cytosolic segments, suggesting that functional Ca²⁺ regulation may be more nuanced. Resolving this ambiguity is critical as CaM is enriched in subcellular domains where Ca_V</

SUBMITTER: Chakouri N 

PROVIDER: S-EPMC7606677 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature