Defective Glycosylation of Dystroglycan in Muscular Dystrophy and Cancer

Part of the Protein Reviews book series (PRON, volume 13)


Dystroglycan is a major cell surface receptor for extracellular matrix (ECM) proteins, including laminins, agrin, and perlecan, and glycosylation of dystroglycan by genes involved in the synthesis of its O-linked mannosyl glycans is necessary for ECM binding. Consistent with an essential role for these carbohydrate structures, loss of function mutations in genes affecting O-linked mannose biosynthesis give rise to forms of congenital and limb-girdle muscular dystrophy, and these can be mimicked by tissue-specific loss of dystroglycan in affected tissues. Because these diseases correlate with loss of dystroglycan glycosylation and function, they are referred to as the dystroglycanopathies. While mutations in all genes known to give rise to dystroglycanopathies have been shown to affect dystroglycan glycosylation, the function of some of these genes remains unknown. Dystroglycan also shows altered glycosylation or proteolytic processing, or decreased expression, in many types of cancer. Because proper glycosylation of dystroglycan is essential for ECM binding, such changes may alter cancer cell growth rate or the propensity of tumors to undergo metastasis. Increasingly, dystroglycan is also being shown to be a receptor or co-receptor for ECM-mediated signal transduction. Therefore, its role in disease may relate to its effects on signaling as well as to its more well-known structural roles in mediating cell-ECM interactions.


Muscular Dystrophy Oral Squamous Cell Carcinoma Congenital Muscular Dystrophy Lassa Fever Sarcolemmal Membrane 


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Departments of Pediatrics and of Physiology and Cell Biology, Center for Gene Therapy, The Research Institute at Nationwide Children’s HospitalOhio State University College of MedicineColumbusUSA

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