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First published online 3 March 2009
doi: 10.1242/jcs.040121

Journal of Cell Science 122, 947-956 (2009)
Published by The Company of Biologists 2009
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Research Article

TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin

Marjorie Coisy-Quivy1,2, Olivia Touzet1,2, Annick Bourret1,2, Robert A. Hipskind3, Jacques Mercier1,2, Philippe Fort4,5 and Alexandre Philips1,2,*

1 INSERM, ERI 25, `Muscle and Pathologies', F-34295 Montpellier, France
2 Université Montpellier I, EA4202, F-34295 Montpellier, France
3 IGMM, CNRS-UMR5535, 1919 route de Mende, F-34293 Montpellier, France
4 Universités Montpellier II et I, Centre de Recherche en Biologie Macromoléculaire, F-34293, Montpellier, France
5 CNRS, UMR5237, 1919 Route de Mende, F-34293 Montpellier, France

* Author for correspondence (e-mail: alexandre.philips{at}inserm.fr)

Accepted 25 November 2008

The contractile activity of striated muscle depends on myofibrils that are highly ordered macromolecular complexes. The protein components of myofibrils are well characterized, but it remains largely unclear how signaling at the molecular level within the sarcomere and the control of assembly are coordinated. We show that the Rho GTPase TC10 appears during differentiation of human primary skeletal myoblasts and it is active in differentiated myotubes. We identify obscurin, a sarcomere-associated protein, as a specific activator of TC10. Indeed, TC10 binds directly to obscurin via its predicted RhoGEF motif. Importantly, we demonstrate that obscurin is a specific activator of TC10 but not the Rho GTPases Rac and Cdc42. Finally, we show that inhibition of TC10 activity by expression of a dominant-negative mutant or its knockdown by expression of specific shRNA block myofibril assembly. Our findings reveal a novel signaling pathway in human skeletal muscle that involves obscurin and the Rho GTPase TC10 and implicate this pathway in new sarcomere formation.

Key words: Myofibrillogenesis, Rho GTPase, Obscurin


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[Abstract] [Full Text] [PDF]


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