Integrin-dependent neuroblastoma cell adhesion and migration on laminin is regulated by expression levels of two enzymes in the O-mannosyl-linked glycosylation pathway, PomGnT1 and GnT-Vb

Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30605, USA.
Experimental Cell Research (Impact Factor: 3.25). 10/2006; 312(15):2837-50. DOI: 10.1016/j.yexcr.2006.05.022
Source: PubMed


O-mannosyl-linked glycans constitute a third of all brain O-linked glycoproteins, and yet very little is understood about their functions. Several congenital muscular dystrophies with central nervous system defects are caused by genetic disruptions in glycosyltransferases responsible for the synthesis of O-mannosyl glycans. The glycosyltransferase GnT-Vb, also known as GnT-IX, is expressed abundantly in the brain and testis and is proposed to be the enzyme that branches O-mannosyl-linked glycans. In this study, we show in a human neuronal model that GnT-Vb expression enhances neurite outgrowth on laminin. GnT-Vb has been shown to perform both N-linked and O-mannosyl-linked glycosylation. To determine if the effect on neurite outgrowth was due to N-linked or O-mannosyl-linked glycosylation by GnT-Vb we suppressed the expression of glycosyltransferases important for the elongation of both N-linked and O-mannosyl-linked glycans using RNA interference. Our results suggest that GnT-Vb and PomGnT1, enzymes involved in the O-mannosyl glycosylation pathway, play an active role in modulating integrin and laminin-dependent adhesion and migration of human neuronal cells.

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    • "Pomgnt1. The enzyme O-mannose beta-1, 2-N-acetylgluco- saminyltransferase participates in O-mannosyl glycan synthesis and has been shown to function in diverse roles including reactive gliosis in the retina, neuroblastoma adhesion (Abbott et al. 2006), muscle-eye-brain disease (Manya et al. 2003, 2004) and the proliferation of myoblasts (Miyagoe-Suzuki "
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    • "For example , knockout of GnT-Va in mouse embryo fibroblasts caused the altered gene expression of other glycosyltransferases and membrane proteins such as β1 integrins (Guo et al. 2005) and galectins (Guo et al. 2008). Furthermore, the increased gene expression of integrins was also observed in SH-SY5Y cells after GnT-Vb knockdown by siRNA (Abbott et al. 2006). A study using GnT-Va null polyoma middle T-induced tumor cells (Lajoie et al. 2007) showed a reduction in the expression of caveolin-1, a coat protein of caveolae mediating endocytosis of some types of receptors. "
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