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Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.

ABSTRACT: Excitation-contraction (EC) coupling comprises events in muscle that convert electrical signals to Ca(2+) transients, which then trigger contraction of the sarcomere. Defects in these processes cause a spectrum of muscle diseases. We report that STAC3, a skeletal muscle-specific protein that localizes to T tubules, is essential for coupling membrane depolarization to Ca(2+) release from the sarcoplasmic reticulum (SR). Consequently, homozygous deletion of src homology 3 and cysteine rich domain 3 (Stac3) in mice results in complete paralysis and perinatal lethality with a range of musculoskeletal defects that reflect a blockade of EC coupling. Muscle contractility and Ca(2+) release from the SR of cultured myotubes from Stac3 mutant mice could be restored by application of 4-chloro-m-cresol, a ryanodine receptor agonist, indicating that the sarcomeres, SR Ca(2+) store, and ryanodine receptors are functional in Stac3 mutant skeletal muscle. These findings reveal a previously uncharacterized, but required, component of the EC coupling machinery of skeletal muscle and introduce a candidate for consideration in myopathic disorders.

SUBMITTER: Nelson BR

PROVIDER: S-EPMC3718085 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.

Nelson Benjamin R BR Wu Fenfen F Liu Yun Y Anderson Douglas M DM McAnally John J Lin Weichun W Cannon Stephen C SC Bassel-Duby Rhonda R Olson Eric N EN

Proceedings of the National Academy of Sciences of the United States of America 20130701 29

Excitation-contraction (EC) coupling comprises events in muscle that convert electrical signals to Ca(2+) transients, which then trigger contraction of the sarcomere. Defects in these processes cause a spectrum of muscle diseases. We report that STAC3, a skeletal muscle-specific protein that localizes to T tubules, is essential for coupling membrane depolarization to Ca(2+) release from the sarcoplasmic reticulum (SR). Consequently, homozygous deletion of src homology 3 and cysteine rich domain ...[more]

PMID: 23818578

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Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.

Publications

Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.

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