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.
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.
Abbott
Karen L
KL
Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30605, USA.
Troupe
Karolyn
K
Lee
Intaek
I
Pierce
Michael
M
D002448:Cell Adhesion; D002465:Cell Movement; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016023:Integrins; D007797:Laminin; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D012313:RNA; C479741:MGAT5B protein, human; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase