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Defective Glycosylation of Dystroglycan in Muscular Dystrophy and Cancer

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Post-Translational Modifications in Health and Disease

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

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Abstract

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.

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  1. Departments of Pediatrics and of Physiology and Cell Biology, Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital, Ohio State University College of Medicine, 700 Children’s Drive, Columbus, OH, 43205, USA

    Paul T. Martin

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  1. Federica Montanaro
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    Cecilio J. Vidal

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Montanaro, F., Martin, P.T. (2011). Defective Glycosylation of Dystroglycan in Muscular Dystrophy and Cancer. In: Vidal, C. (eds) Post-Translational Modifications in Health and Disease. Protein Reviews, vol 13. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6382-6_6

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