期刊
JOURNAL OF CELL BIOLOGY
卷 217, 期 2, 页码 685-700出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201705130
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资金
- Association Francaise contre les Myopathies [20975]
- Labex WhoAmI?
- Idex Sorbonne Paris Cite
- Agence Nationale de la Recherche [ANR-13-BSV1-MECHANO, ANR-14-CE12-0001-01]
Satellite cells (SCs) are adult muscle stem cells that are mobilized when muscle homeostasis is perturbed. Here, we show that serum response factor (Srf) is needed for optimal SC-mediated hypertrophic growth. We identified Srf as a master regulator of SC fusion required in both fusion partners, whereas it was dispensable for SC proliferation and differentiation. We show that SC-specific Srf deletion leads to impaired actin cytoskeleton and report the existence of finger-like actin-based protrusions at fusion sites in vertebrates that were notoriously absent in fusion-defective myoblasts lacking Srf. Restoration of a polymerized actin network by overexpression of an a-actin isoform in Srf mutant SCs rescued their fusion with a control cell in vitro and in vivo and reestablished overload-induced muscle growth. These findings demonstrate the importance of Srf in controlling the organization of actin cytoskeleton and actin-based protrusions for myoblast fusion in mammals and its requirement to achieve efficient hypertrophic myofiber growth.
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