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Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex
Journal article   Open access   Peer reviewed

Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex

Aaron M Beedle, Patricia M Nienaber and Kevin P Campbell
The Journal of biological chemistry, Vol.282(23), pp.16713-16717
06/08/2007
DOI: 10.1074/jbc.C700061200
PMID: 17452335
url
https://doi.org/10.1074/jbc.C700061200View
Published (Version of record) Open Access

Abstract

Mutations in fukutin-related protein (FKRP) give rise to mild and more severe forms of muscular dystrophy. FKRP patients have reduced glycosylation of the extracellular protein dystroglycan, and FKRP itself shows sequence similarity to glycosyltransferases, implicating FKRP in the processing of dystroglycan. However, FKRP localization is controversial, and no FKRP complexes are known, so any FKRP-dystroglycan link remains elusive. Here, we demonstrate a novel FKRP localization in vivo; in mouse, both endogenous and recombinant FKRP are present at the sarcolemma. Biochemical analyses revealed that mouse muscle FKRP and dystroglycan co-enrich and co-fractionate, indicating that FKRP coexists with dystroglycan in the native dystrophin-glycoprotein complex. Furthermore, FKRP sedimentation shifts with dystroglycan in disease models involving the dystrophin-glycoprotein complex, and sarcolemmal FKRP immunofluorescence mirrors that of dystroglycan in muscular dystrophy mice, suggesting that FKRP localization may be mediated by dystroglycan. These data offer the first evidence of an FKRP complex in muscle and suggest that FKRP may influence the glycosylation status of dystroglycan from within the sarcolemmal dystrophin-glycoprotein complex.
 Animals Proteins - metabolism Mice, Inbred C57BL Transferases Fluorescent Antibody Technique Glycoproteins - metabolism Mice Dystrophin - metabolism Sarcolemma - metabolism

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