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  Defective integrin switch and matrix composition at alpha 7- deficient myotendinous junctions precede the onset of muscular dystrophy in mice

Nawrotzki, R., Willem, M., Miosge, N., Brinkmeier, H., & Mayer, U. (2003). Defective integrin switch and matrix composition at alpha 7- deficient myotendinous junctions precede the onset of muscular dystrophy in mice. Human Molecular Genetics, 12(5), 483-495.

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Genre: Journal Article
Alternative Title : Hum. Mol. Genet.

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Nawrotzki, R., Author
Willem, M.1, Author              
Miosge, N., Author
Brinkmeier, H., Author
Mayer, U.1, Author              
Affiliations:
1Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2003-03-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 41656
ISI: 000181379600004
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Title: Human Molecular Genetics
  Alternative Title : Hum. Mol. Genet.
Source Genre: Journal
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Affiliations:
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Pages: - Volume / Issue: 12 (5) Sequence Number: - Start / End Page: 483 - 495 Identifier: ISSN: 0964-6906