Physical interaction of junctophilin and the Ca_V1.1 C terminus is crucial for skeletal muscle contraction.

ABSTRACT: Close physical association of Ca_V1.1 L-type calcium channels (LTCCs) at the sarcolemmal junctional membrane (JM) with ryanodine receptors (RyRs) of the sarcoplasmic reticulum (SR) is crucial for excitation-contraction coupling (ECC) in skeletal muscle. However, the molecular mechanism underlying the JM targeting of LTCCs is unexplored. Junctophilin 1 (JP1) and JP2 stabilize the JM by bridging the sarcolemmal and SR membranes. Here, we examined the roles of JPs in localization and function of LTCCs. Knockdown of JP1 or JP2 in cultured myotubes inhibited LTCC clustering at the JM and suppressed evoked Ca²⁺ transients without disrupting JM structure. Coimmunoprecipitation and GST pull-down assays demonstrated that JPs physically interacted with 12-aa residues in the prox

SUBMITTER: Nakada T 

PROVIDER: S-EPMC5924888 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature