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

Benjamin R. Nelson, Fenfen Wu, Yun Liu, Douglas M. Anderson, John Mcanally, Weichun Lin, Stephen C. Cannon, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Excitation-contraction (EC) coupling comprises events in muscle that convert electrical signals to Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)11881-11886
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number29
DOIs
StatePublished - Jul 16 2013

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Excitation Contraction Coupling
Sarcoplasmic Reticulum
Sarcomeres
Ryanodine Receptor Calcium Release Channel
Skeletal Muscle
Muscles
Proteins
Muscle Proteins
Skeletal Muscle Fibers
Paralysis
Cysteine
Membranes

Keywords

  • Dihydropyridine Receptor
  • Dysgenic
  • Dyspedic
  • Myopathy
  • Neuromuscular Junction

ASJC Scopus subject areas

  • General

Cite this

Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility. / Nelson, Benjamin R.; Wu, Fenfen; Liu, Yun; Anderson, Douglas M.; Mcanally, John; Lin, Weichun; Cannon, Stephen C.; Bassel-Duby, Rhonda; Olson, Eric N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 29, 16.07.2013, p. 11881-11886.

Research output: Contribution to journalArticle

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