| First Author | Inamori KI | Year | 2016 |
| Journal | Glycobiology | Volume | 26 |
| Issue | 12 | Pages | 1284-1296 |
| PubMed ID | 27496765 | Mgi Jnum | J:348635 |
| Mgi Id | MGI:6198855 | Doi | 10.1093/glycob/cww075 |
| Citation | Inamori KI, et al. (2016) LARGE2-dependent glycosylation confers laminin-binding ability on proteoglycans. Glycobiology 26(12):1284-1296 |
| abstractText | Both LARGE1 (formerly LARGE) and its paralog LARGE2 are bifunctional glycosyltransferases with xylosy- and glucuronyltransferase activities, and are capable of synthesizing polymers composed of a repeating disaccharide [-3Xylalpha1,3GlcAbeta1-]. Post-translational modification of the O-mannosyl glycan of alpha-dystroglycan (alpha-DG) with the polysaccharide is essential for it to act as a receptor for ligands in the extracellular matrix (ECM), and both LARGE paralogs contribute to the modification in vivo. LARGE1 and LARGE2 have different tissue distribution profiles and enzymatic properties; however, the functional difference of the homologs remains to be determined, and alpha-DG is the only known substrate for the modification by LARGE1 or LARGE2. Here we show that LARGE2 can modify proteoglycans (PGs) with the laminin-binding glycan. We found that overexpression of LARGE2, but not LARGE1, mediates the functional modification on the surface of DG(-/-), Pomt1(-/-) and Fktn(-/-) embryonic stem cells. We identified a heparan sulfate-PG glypican-4 as a substrate for the LARGE2-dependent modification by affinity purification and subsequent mass spectrometric analysis. Furthermore, we showed that LARGE2 could modify several additional PGs with the laminin-binding glycan, most likely within the glycosaminoglycan (GAG)-protein linkage region. Our results indicate that LARGE2 can modify PGs with the GAG-like polysaccharide composed of xylose and glucuronic acid to confer laminin binding. Thus, LARGE2 may play a differential role in stabilizing the basement membrane and modifying its functions by augmenting the interactions between laminin globular domain-containing ECM proteins and PGs. |
