STIM1-Ca(2+) signaling is required for the hypertrophic growth of skeletal muscle in mice.

Journal Article

Immediately after birth, skeletal muscle must undergo an enormous period of growth and differentiation that is coordinated by several intertwined growth signaling pathways. How these pathways are integrated remains unclear but is likely to involve skeletal muscle contractile activity and calcium (Ca(2+)) signaling. Here, we show that Ca(2+) signaling governed by stromal interaction molecule 1 (STIM1) plays a central role in the integration of signaling and, therefore, muscle growth and differentiation. Conditional deletion of STIM1 from the skeletal muscle of mice (mSTIM1(-/-) mice) leads to profound growth delay, reduced myonuclear proliferation, and perinatal lethality. We show that muscle fibers of neonatal mSTIM1(-/-) mice cannot support the activity-dependent Ca(2+) transients evoked by tonic neurostimulation, even though excitation contraction coupling (ECC) remains unperturbed. In addition, disruption of tonic Ca(2+) signaling in muscle fibers attenuates downstream muscle growth signaling, such as that of calcineurin, mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1 and 2 (ERK1/2), and AKT. Based on our findings, we propose a model wherein STIM1-mediated store-operated calcium entry (SOCE) governs the Ca(2+) signaling required for cellular processes that are necessary for neonatal muscle growth and differentiation.

Full Text

Duke Authors

Cited Authors

  • Li, T; Finch, EA; Graham, V; Zhang, Z-S; Ding, J-D; Burch, J; Oh-hora, M; Rosenberg, P

Published Date

  • August 2012

Published In

Volume / Issue

  • 32 / 15

Start / End Page

  • 3009 - 3017

PubMed ID

  • 22645307

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.06599-11

Language

  • eng

Conference Location

  • United States