Editors' ChoiceBiochemistry

Modifying Protein Modification

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Science Signaling  05 Jan 2010:
Vol. 3, Issue 103, pp. ec6
DOI: 10.1126/scisignal.3103ec6

α-dystroglycan is a cell surface receptor that anchors the basal lamina to the sarcolemma by binding proteins containing laminin-G domains. This binding is essential for protecting muscle from contraction-induced injury, and defective binding is thought to cause a subclass of congenital muscular dystrophy (CMD) in humans. Mutations in six (putative) glycosyltransferase genes have been identified in patients with CMD, suggesting that they participate in the posttranslational modification of α-dystroglycan that confers the ability to bind laminin. Despite extensive efforts for more than 20 years, the actual laminin-binding moiety remained unclear. Here, Yoshida-Moriguchi et al. identified a phosphorylated O-mannosyl glycan on α-dystroglycan. This modification occurred in the Golgi by an unidentified kinase and was required for the maturation of α-dystroglycan into its laminin-binding form. These findings facilitate our understanding of the mechanisms that underlie CMD and expand our knowledge of mammalian protein glycosylation.

T. Yoshida-Moriguchi, L. Yu, S. H. Stalnaker, S. Davis, S. Kunz, M. Madson, M. B. A. Oldstone, H. Schachter, L. Wells, K. P. Campbell, O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding. Science 327, 88–92 (2010). [Abstract] [Full Text]

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