| First Author | Nawrotzki R | Year | 2003 |
| Journal | Hum Mol Genet | Volume | 12 |
| Issue | 5 | Pages | 483-95 |
| PubMed ID | 12588796 | Mgi Jnum | J:82116 |
| Mgi Id | MGI:2451190 | Doi | 10.1093/hmg/ddg047 |
| Citation | Nawrotzki R, et al. (2003) Defective integrin switch and matrix composition at alpha 7-deficient myotendinous junctions precede the onset of muscular dystrophy in mice. Hum Mol Genet 12(5):483-95 |
| abstractText | 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. |
