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J. Biol. Chem., Vol. 282, Issue 11, 8393-8403, March 16, 2007

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Two Novel Members of the ABLIM Protein Family, ABLIM-2 and -3, Associate with STARS and Directly Bind F-actin^*

Tomasa Barrientos¹², Derk Frank¹³, Koichiro Kuwahara, Svetlana Bezprozvannaya, G. C. Teg Pipes, Rhonda Bassel-Duby, James A. Richardson^¶, Hugo A. Katus, Eric N. Olson, and Norbert Frey⁴

From the Departments of Molecular Biology and ^¶Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148 and the Department of Internal Medicine III, University of Heidelberg, 69115 Heidelberg, Germany

In addition to regulating cell motility, contractility, and cytokinesis, the actin cytoskeleton plays a critical role in the regulation of transcription and gene expression. We have previously identified a novel muscle-specific actin-binding protein, STARS (striated muscle activator of Rho signaling), which directly binds actin and stimulates serum-response factor (SRF)-dependent transcription. To further dissect the STARS/SRF pathway, we performed a yeast two-hybrid screen of a skeletal muscle cDNA library using STARS as bait, and we identified two novel members of the ABLIM protein family, ABLIM-2 and -3, as STARS-interacting proteins. ABLIM-1, which is expressed in retina, brain, and muscle tissue, has been postulated to function as a tumor suppressor. ABLIM-2 and -3 display distinct tissue-specific expression patterns with the highest expression levels in muscle and neuronal tissue. Moreover, these novel ABLIM proteins strongly bind F-actin, are localized to actin stress fibers, and synergistically enhance STARS-dependent activation of SRF. Conversely, knockdown of endogenous ABLIM expression utilizing small interfering RNA significantly blunted SRF-dependent transcription in C2C12 skeletal muscle cells. These findings suggest that the members of the novel ABLIM protein family may serve as a scaffold for signaling modules of the actin cytoskeleton and thereby modulate transcription.

Received for publication, August 8, 2006 , and in revised form, December 7, 2006.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) DQ413177 [GenBank] , DQ413176 [GenBank] , DQ413175 [GenBank] , DQ413174 [GenBank] .

^* This work was supported in part by grants from the National Institute of Health, the D. W. Reynolds Cardiovascular Clinical Research Center, the Texas Advanced Technology Program, and the Robert A. Welch Foundation (to E. N. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1 and 2.

¹ Both authors contributed equally to this work.

² Supported by a National Institutes of Health minority supplement grant.

³ Supported by the Young Investigator Program of the University of Heidelberg.

⁴ Supported by the Bundesministerium für Bildung und Forschung, Germany, Grant GFN2-Nationales Genomforschungsnetz. To whom correspondence may be addressed. Tel.: 49 6221-56-1505; Fax: 49-6221-56-8647; E-mail: Norbert.Frey{at}med.uni-heidelberg.de.

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