Sci. Signal., 5 January 2010
Biochemistry Modifying Protein Modification
Science, AAAS, Washington, DC 20005, USA
-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 -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 -dystroglycan. This modification occurred in the Golgi by an unidentified kinase and was required for the maturation of -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]
Citation: H. Pickersgill, Modifying Protein Modification. Sci. Signal. 3, ec6 (2010).
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