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

J. Biol. Chem., Vol. 282, Issue 21, 15730-15742, May 25, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/21/15730    most recent M611197200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Samson, T. Articles by Wixler, V. Search for Related Content PubMed PubMed Citation Articles by Samson, T. Articles by Wixler, V. Social Bookmarking                      What's this?

Def-6, a Guanine Nucleotide Exchange Factor for Rac1, Interacts with the Skeletal Muscle Integrin Chain 7A and Influences Myoblast Differentiation^*

Thomas Samson¹, Carola Will, Alexander Knoblauch, Lisa Sharek, Klaus von der Mark^¶, Keith Burridge², and Viktor Wixler²

From the Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, the Institut für Molekulare Virologie, Zentrum für Molekularbiologie der Entzündung, Universitätsklinikum Münster, 48149 Münster, Germany, and the ^¶Experimentelle Medizin I, Nikolaus-Fiebiger Zentrum, Universität Erlangen-Nürnberg, 91054 Erlangen, Germany

Integrin 71 is the major laminin binding integrin receptor of muscle cells. The 7 chain occurs in several splice isoforms, of which 7A and 7B differ in their intracellular domains only. The fact that the expression of 7A and 7B is tightly regulated during skeletal muscle development suggests different and distinct roles for both isoforms. However, so far, functional properties and interacting proteins were described for the 7B chain only. Using a yeast two-hybrid screen, we have found that Def-6, a guanine nucleotide exchange factor for Rac1, binds to the intracellular domain of the 7A subunit. The specificity of the Def-6-7A interaction has been shown by direct yeast two-hybrid binding assays and coprecipitation experiments. This is the first description of an 7A-specific and -exclusive interaction, because Def-6 did not bind to any other tested integrin cytoplasmic domain. Interestingly, the binding of Def-6 to 7A was abolished, when cells were cotransfected with an Src-related kinase, which is known to phosphorylate Def-6 and stimulate its exchange activity. We found expression of Def-6 was not only restricted to T-lymphocytes as described thus far but in a more widespread manner, including different muscle tissues. In cells, Def-6 is seen in newly forming cell protrusions and focal adhesions, and its localization partially overlaps with the 7A integrin receptor. C2C12 myoblasts overexpressing Def-6 show a delay of Rac1 inactivation during myogenic differentiation and abnormal myotube formation. Thus, our data suggest a role for Def-6 in the fine regulation of Rac1 during myogenesis with the integrin 7A chain guiding this regulation in a spatio-temporal manner.

Received for publication, December 6, 2006 , and in revised form, March 23, 2007.

^* This work was supported by the Deutsche Forschungsgemeinschaft (DFG) Sa 1636/1-1 (to T. S.) and DFG Wi 1235/4-1 (to V. W.) and by National Institutes of Health Grant GM29860 (to K. B.). 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.

² Both authors contributed equally to this work.

¹ To whom correspondence should be addressed: Dept. of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, CB#7295, University of North Carolina, Chapel Hill, NC 27599. Tel.: 919-966-5783; Fax: 919-966-3015; E-mail: thomas_samson{at}med.unc.edu.

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

This article has been cited by other articles:

				K. V. Pajcini, J. H. Pomerantz, O. Alkan, R. Doyonnas, and H. M. Blau Myoblasts and macrophages share molecular components that contribute to cell-cell fusion J. Cell Biol., March 5, 2008; 180(5): 1005 - 1019. [Abstract] [Full Text] [PDF]