STAC3 stably interacts through its C1 domain with Ca_V1.1 in skeletal muscle triads.

ABSTRACT: The adaptor protein STAC3 is essential for skeletal muscle excitation-contraction (EC) coupling and a mutation in the STAC3 gene has been linked to a severe muscle disease, Native American myopathy (NAM). However the function of STAC3, its interaction partner, and the mode of interaction within the EC-coupling complex remained elusive. Here we demonstrate that STAC3 forms a stable interaction with the voltage-sensor of EC-coupling, Ca_V1.1, and that this interaction depends on a hitherto unidentified protein-protein binding pocket in the C1 domain of STAC3. While the NAM mutation does not affect the stability of the STAC3-Ca_V1.1 interaction, mutation of two crucial residues in the C1 binding pocket increases the turnover of STAC3 in skeletal muscle triads. Thus, the C1

SUBMITTER: Campiglio M 

PROVIDER: S-EPMC5253670 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature