Alterations of dystrophin-associated glycoproteins in the heart lacking dystrophin or dystrophin and utrophin

Katharine M Sharpe, Monica D. Premsukh, DeWayne Townsend

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Heart disease is a leading cause of death in patients with Duchenne muscular dystrophy (DMD). Patients with DMD lack the protein dystrophin, which is widely expressed in striated muscle. In skeletal muscle, the loss of dystrophin results in dramatically decreased expression of the dystrophin associated glycoprotein complex (DGC). Interestingly, in the heart the DGC is normally expressed without dystrophin; this has been attributed to presence of the dystrophin homologue utrophin. We demonstrate here that neither utrophin nor dystrophin are required for the expression of the cardiac DGC. However, alpha-dystroglycan (α-DG), a major component of the DGC, is differentially glycosylated in dystrophin-(mdx) and dystrophin-/utrophin-(dko) deficient mouse hearts. In both models the altered α-DG retains laminin binding activity, but has an altered localization at the sarcolemma. In hearts lacking both dystrophin and utrophin, the alterations in α-DG glycosylation are even more dramatic with changes in gel migration equivalent to 24 ± 3 kDa. These data show that the absence of dystrophin and utrophin alters the processing of α-DG; however it is not clear if these alterations are a consequence of the loss of a direct interaction with dystrophin/utrophin or results from an indirect response to the presence of severe pathology. Recently there have been great advances in our understanding of the glycosylation of α-DG regarding its role as a laminin receptor. Here we present data that alterations in glycosylation occur in the hearts of animal models of DMD, but these changes do not affect laminin binding. The physiological consequences of these alterations remain unknown, but may have significant implications for the development of therapies for DMD.

Original languageEnglish (US)
Pages (from-to)395-405
Number of pages11
JournalJournal of muscle research and cell motility
Volume34
Issue number5-6
DOIs
StatePublished - Dec 2013

Keywords

  • Alpha-dystroglycan
  • Dystrophic cardiomyopathy
  • Dystrophin
  • Glycosylation
  • Utrophin

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