Editors' ChoiceBiochemistry

Dissecting Dystrophies

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Sci. Signal.  27 Aug 2013:
Vol. 6, Issue 290, pp. ec205
DOI: 10.1126/scisignal.2004672

Defects in α-dystroglycan lead to various congenital muscular dystrophies, and its ability to bind to extracellular matrix (ECM) is dependent on formation of a specific O-linked sugar structure. Previous efforts to understand the molecular mechanisms underlying α-dystroglycan’s ability to bind to the ECM led to the identification of a phosphorylated O-mannosyl trisaccharide on α-dystroglycan and to the demonstration that addition of this residue is a prerequisite for formation of the ligand-binding motif. However, the biosynthetic pathway that leads to production of the phosphorylated O-mannosyl glycan has not been delineated. Yoshida-Moriguchi et al. elucidate the functions of three genes recently found to cause dystroglycan-related disorders and explain the defects in the production of the phosphorylated O-mannosyl glycan that underlie the pathologies of patients with the relevant mutations.

T. Yoshida-Moriguchi, T. Willer, M. E. Anderson, D. Venzke, T. Whyte, F. Muntoni, H. Lee, S. F. Nelson, L. Yu, K. P. Campbell, SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science 341, 896–899 (2013). [Abstract] [Full Text]