HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 15, 9996-10001, April 14, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/15/9996    most recent M513121200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rybakova, I. N. Articles by Ervasti, J. M. Search for Related Content PubMed PubMed Citation Articles by Rybakova, I. N. Articles by Ervasti, J. M. Social Bookmarking                      What's this?

Dystrophin and Utrophin Bind Actin through Distinct Modes of Contact^*

From the Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53706

This study was designed to define the molecular epitopes of dystrophin-actin interaction and to directly compare the actin binding properties of dystrophin and utrophin. According to our data, dystrophin and utrophin both bound alongside actin filaments with submicromolar affinities. However, the molecular epitopes involved in actin binding differed between the two proteins. In utrophin, the amino-terminal domain and an adjacent string of the first 10 spectrin-like repeats more fully recapitulated the activities measured for full-length protein. The homologous region of dystrophin bound actin with low affinity and near 1:1 stoichiometry as previously measured for the isolated amino-terminal, tandem (CH) domain. In contrast, a dystrophin construct including a cluster of basic spectrin-like repeats and spanning from the amino terminus through repeat 17, bound actin with properties most similar to full-length dystrophin. Dystrophin and utrophin both stabilized preformed actin filaments from forced depolymerization with similar efficacies but did not appear to compete for binding sites on actin. We also found that dystrophin binding to F-actin was markedly sensitive to increasing ionic strength, although utrophin binding was unaffected. Although dystrophin and utrophin are functionally homologous actin-binding proteins, these results indicate that their respective modes of contact with actin filaments are markedly different. Finally, we reassessed the abundance of dystrophin in striated muscle using full-length protein as the standard and measured greater than 10-fold higher values than previously reported.

Received for publication, December 8, 2005 , and in revised form, February 9, 2006.

^* This study was supported by an American Heart Association Scientist development grant (to I. N. R.), American Heart Association Predoctoral Fellowship (to K. J. S.), and National Institutes of Health Grant ARO42423 (to J. M. E.). 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.

¹ To whom correspondence should be addressed: Dept. of Physiology, University of Wisconsin, 127 Service Memorial Institute, 1300 University Ave., Madison, WI 53706. Tel.: 608-265-3419; Fax: 608-265-5512; E-mail: ervasti{at}physiology.wisc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Prochniewicz, D. Henderson, J. M. Ervasti, and D. D. Thomas Dystrophin and utrophin have distinct effects on the structural dynamics of actin PNAS, May 12, 2009; 106(19): 7822 - 7827. [Abstract] [Full Text] [PDF]

				G. B. Banks, P. Gregorevic, J. M. Allen, E. E. Finn, and J. S. Chamberlain Functional capacity of dystrophins carrying deletions in the N-terminal actin-binding domain Hum. Mol. Genet., September 1, 2007; 16(17): 2105 - 2113. [Abstract] [Full Text] [PDF]

				G. A. Rezniczek, P. Konieczny, B. Nikolic, S. Reipert, D. Schneller, C. Abrahamsberg, K. E. Davies, S. J. Winder, and G. Wiche Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with {beta}-dystroglycan J. Cell Biol., March 26, 2007; 176(7): 965 - 977. [Abstract] [Full Text] [PDF]

				P. Martinez-Martinez, M. Losen, H. Duimel, P. Frederik, F. Spaans, P. Molenaar, A. Vincent, and M. H. De Baets Overexpression of Rapsyn in Rat Muscle Increases Acetylcholine Receptor Levels in Chronic Experimental Autoimmune Myasthenia Gravis Am. J. Pathol., February 1, 2007; 170(2): 644 - 657. [Abstract] [Full Text] [PDF]