STIM1-Ca2+ Signaling Is Required for the Hypertrophic Growth of Skeletal Muscle in Mice

Tianyu Li, Elizabeth A. Finch, Victoria Graham, Zhu Shan Zhang, Jin Dong Ding, Jarrett Burch, Masatsugu Oh-hora, Paul Rosenberg

    Research output: Contribution to journalArticlepeer-review

    54 Citations (Scopus)

    Abstract

    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 (Ca2+) signaling. Here, we show that Ca2+ 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 activitydependent Ca2+ transients evoked by tonic neurostimulation, even though excitation contraction coupling (ECC) remains unperturbed. In addition, disruption of tonic Ca2+ 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 Ca2+ signaling required for cellular processes that are necessary for neonatal muscle growth and differentiation.

    Original languageEnglish
    Pages (from-to)3009-3017
    Number of pages9
    JournalMolecular and cellular biology
    Volume32
    Issue number15
    DOIs
    Publication statusPublished - Aug 2012

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Cell Biology

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