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          Institute: MPI für Biochemie     Collection: Emeriti Groups     Display Documents



ID: 41656.0, MPI für Biochemie / Emeriti Groups
Defective integrin switch and matrix composition at alpha 7- deficient myotendinous junctions precede the onset of muscular dystrophy in mice
Authors:Nawrotzki, R.; Willem, M.; Miosge, N.; Brinkmeier, H.; Mayer, U.
Language:English
Date of Publication (YYYY-MM-DD):2003-03-01
Title of Journal:Human Molecular Genetics
Journal Abbrev.:Hum. Mol. Genet.
Volume:12
Issue / Number:5
Start Page:483
End Page:495
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Force transmission at the myotendinous junction requires a strong link between the muscle cytoskeleton and the extracellular matrix. At the adult junction, two splice variants of the laminin-binding integrins, alpha7Abeta1D and alpha7Bbeta1D, are highly enriched. The alpha7 subunits are critical for the integrity of the junctional sarcolemma because integrin alpha7-deficient mice develop muscular dystrophy, primarily affecting this site of the muscle. Here, we report that beta1D integrin coimmunoprecipitates and colocalizes with the alpha5 subunit at alpha7-deficient junctions, but does not associate with alpha3, alpha6 or alphav integrins. By immunogold labelling we show that the basement membranes of integrin alpha7-deficient muscles recruit abnormally high levels of fibronectin, the ligand of alpha5beta1D. Finally, we demonstrate that alpha5beta1D is down-regulated at the normal postnatal junction and is displaced by alpha7beta1D. These results suggest that the alpha7 subunit is implicated in the down-regulation of alpha5beta1D and in the removal of fibronectin from the maturing myotendinous junction, thus providing an alpha7beta1D-based link to laminin. We propose that the persistence of alpha5beta1D in alpha7-deficient mice is not compatible with normal muscle function and leads to muscle wasting.
Comment of the Author/Creator:Date: 2003, MAR 1
External Publication Status:published
Document Type:Article
Communicated by:N.N.
Affiliations:MPI für Biochemie/Emeriti Groups/Protein Chemistry (R. Timpl)
External Affiliations:Univ Manchester, Sch Biol Sci, Wellcome Trust Ctr Cell Matrix; Res, 3-239 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs,; England; Univ Manchester, Sch Biol Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England; Univ Ulm, Dept Anat & Cellular Neurobiol, D-89069 Ulm, Germany; Univ Gottingen, Dept Histol, D-37075 Gottingen, Germany; Univ Greifswald, Inst Pathophysiol, D-17495 Karlsburg, Germany
Identifiers:ISI:000181379600004 [ID No:1]
ISSN:0964-6906 [ID No:2]
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