These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inhibition of dystroglycan cleavage causes muscular dystrophy in transgenic mice.
    Author: Jayasinha V, Nguyen HH, Xia B, Kammesheidt A, Hoyte K, Martin PT.
    Journal: Neuromuscul Disord; 2003 Jun; 13(5):365-75. PubMed ID: 12798792.
    Abstract:
    Dystroglycan (DG) is an essential component of the dystrophin-glycoprotein complex, a molecular scaffold that links the extracellular matrix to the actin cytoskeleton. Dystroglycan protein is post-translationally cleaved into alpha dystroglycan, a highly glycosylated peripheral membrane protein, and beta dystroglycan, a transmembrane protein. Despite clear evidence of the importance of dystroglycan and its associated proteins in muscular dystrophy, the purpose of dystroglycan proteolysis is unclear. By introducing a point mutation at the normal site of proteolysis (serine 654 to alanine, DGS654A), we have created a dystroglycan protein that is severely inhibited in its cleavage. Transgenic expression of DGS654A in mouse skeletal muscles inhibited the expression of endogenously cleaved dystroglycan, while overexpression of wild type dystroglycan by similar amounts did not. DGS654A animals had increased serum creatine kinase activity and most muscles had increased numbers of central nuclei. Overexpression of wild type dystroglycan, by contrast, caused no dystrophy by these measures. Dystrophy in DGS654A muscles correlated with reduced binding of antibodies that recognize glycosylated forms of alpha dystroglycan. Lastly, neuromuscular junctions in DGS654A muscles were aberrant in structure. These data show that aberrant processing of the dystroglycan polypeptide causes muscular dystrophy and suggest that dystroglycan processing is important for the proper glycosylation of alpha dystroglycan.
    [Abstract] [Full Text] [Related] [New Search]