Dystroglycan Function Requires Xylosyl- and Glucuronyltransferase Activities of LARGE
By K. Inamori, Takako Yoshida-Moriguchi, Y. Hara, Mary E. Anderson, Liping Yu, K. Campbell. 2012
284 citations recorded by the source corpus.
Going LARGE Dystroglycan (DG) is a highly glycosylated extracellular matrix (ECM) receptor involved in a variety of physiological processes, including maintenance of skeletal muscle membrane integrity and the structure and function of the central nervous system. The like-acetylglucosaminyltransferase (LARGE) is responsible for posttranslational modifications of alpha-dystroglycan (α-DG) required for its function. Now, Inamori et al. (p. 93) demonstrate that LARGE is a bifunctional glycosyltransferase able to transfer xylose and glucuronic acid. These modifications allow α-DG to bind the laminin-G domain–containing ECM ligands: laminin, agrin, and neurexin. A bifunctional enzyme adds a heteropolysaccharide to an extracellular matrix receptor, enabling it to bind laminin. Posttranslational modification of alpha-dystroglycan (α-DG) by the like-acetylglucosaminyltransferase (LARGE) is required for it to function as an extracellular matrix (ECM) receptor. Mutations in the LARGE gene have been identified in congenital muscular dystrophy patients with brain abnormalities. However, the precise function of LARGE remains unclear. Here we found that LARGE could act as a bifunctional glycosyltransferase, with both xylosyltransferase and glucuronyltransferase activities, which produced repeating units of [–3-xylose–α1,3-glucuronic acid-β1–]. This modification allowed α-DG to bind laminin-G domain–containing ECM ligands.
Subfields: Cancer Research, Immunology and Allergy, Molecular Biology
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Citations in the corpus
- Biological roles of glycans (2016, background): “To cite just a few examples, the following glycans were mostly unknown when the previous version of this review was being written: functional sialylation in the fly nervous system (181); O-fucose and O-glucose glycans on Notch (182-184), and O-fucose on thrombospondin repeats (185) ; mucin type O-gl”
- Protein Glycosylation in Cancer (2015, background): “the novel mannose 6-phosphate linker (31) to which repeating units of xylose and glucuronate are added (32), again in a protein-specific manner.”