The C2 domains of dysferlin: roles in membrane localization, Ca²⁺ signalling and sarcolemmal repair.

ABSTRACT: Dysferlin is an integral membrane protein of the transverse tubules of skeletal muscle that is mutated or absent in limb girdle muscular dystrophy 2B and Miyoshi myopathy. Here we examine the role of dysferlin's seven C2 domains, C2A through C2G, in membrane repair and Ca²⁺ release, as well as in targeting dysferlin to the transverse tubules of skeletal muscle. We report that deletion of either domain C2A or C2B inhibits membrane repair completely, whereas deletion of C2C, C2D, C2E, C2F or C2G causes partial loss of membrane repair that is exacerbated in the absence of extracellular Ca²⁺ . Deletion of C2C, C2D, C2E, C2F or C2G also causes significant changes in Ca²⁺ release, measured as the amplitude of the Ca²⁺ transient before or after hypo-osm

SUBMITTER: Muriel J 

PROVIDER: S-EPMC9285653 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature