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Molecular and Cellular Biology, April 2005, p. 3173-3181, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3173-3181.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Muscle-Specific Signaling Mechanism That Links Actin Dynamics to Serum Response Factor{dagger}

Koichiro Kuwahara, Tomasa Barrientos, G. C. Teg Pipes, Shijie Li, and Eric N. Olson*

Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Received 28 September 2004/ Returned for modification 7 November 2004/ Accepted 19 January 2005

Myocardin and the myocardin-related transcription factors (MRTFs) MRTF-A and MRTF-B are coactivators for serum response factor (SRF), which regulates genes involved in cell proliferation, migration, cytoskeletal dynamics, and myogenesis. MRTF-A has been shown to translocate to the nucleus and activate SRF in response to Rho signaling and actin polymerization. Previously, we described a muscle-specific actin-binding protein named striated muscle activator of Rho signaling (STARS) that also activates SRF through a Rho-dependent mechanism. Here we show that STARS activates SRF by inducing the nuclear translocation of MRTFs. The STARS-dependent nuclear import of MRTFs requires RhoA and actin polymerization, and the actin-binding domain of STARS is necessary and sufficient for this activity. A knockdown of endogenous STARS expression by using small interfering RNA significantly reduced SRF activity in differentiated C2C12 skeletal muscle cells and cardiac myocytes. The ability of STARS to promote the nuclear localization of MRTFs and SRF-mediated transcription provides a potential muscle-specific mechanism for linking changes in actin dynamics and sarcomere structure with striated muscle gene expression.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd., Dallas, TX 75390. Phone: (214) 648-1187. Fax: (214) 648-1196. E-mail: eric.olson{at}utsouthwestern.edu.

{dagger} We dedicate this paper to the memory of Akiko Arai.

Molecular and Cellular Biology, April 2005, p. 3173-3181, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3173-3181.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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