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FEBS Lett. 2005 Apr 11;579(10):2236-42.

Requirement of the transmembrane semaphorin Sema4C for myogenic differentiation.

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Department of Pharmacology, Yamaguchi University School of Medicine, Yamaguchi University Hospital, Ube, Yamaguchi 755-8505, Japan.


Semaphorins constitute a large family of signaling proteins that contribute to axonal guidance. Here we demonstrate that the transmembrane semaphorin Sema4C is up-regulated both in the early stage of differentiation of C2C12 mouse skeletal myoblasts into myotubes and during injury-induced muscle regeneration in vivo. Depletion of Sema4C in C2C12 cells resulted in marked attenuation of myotube formation. A fusion protein containing the extracellular Sema domain and a peptide corresponding to the intracellular COOH-terminal region of Sema4C each inhibited the differentiation of C2C12 cells. These findings indicate that Sema4C-mediated interaction among myoblasts plays an important role in terminal myogenic differentiation.

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