Functional roles of the bisecting GlcNAc in integrin-mediated cell adhesion.
N-acetylglucosaminyltransferase III (GnT-III) transfers N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to core mannose with a beta1,4 linkage, so-called bisecting GlcNAc, in N-glycans. The bisecting GlcNAc is found in various hybrid and complex N-glycans. GnT-III is generally regarded as a key glycosyltransferase in N-glycan biosynthetic pathways. Introduction of a bisecting GlcNAc suppresses further processing and elongation of N-glycans catalyzed by other GlcNAc transferases to form branching structures, such as N-acetylglucosaminyltransferase V (GnT-V), since GnT-V cannot utilize the bisected oligosaccharide as a substrate. Considering that expression of the enzyme leads to a remarkable structural alteration of the N-glycans on cell surface, it has been postulated that the enzyme is associated with various biological events such as cell adhesion, migration, cell growth, cell differentiation, and tumor invasion. Integrin is a major carrier of N-glycans. In fact, overexpression of GnT-III reduced the beta1,6 GlcNAc branching structures, in conjunction with the increase in the bisected N-glycans on integrins, and resulted in an inhibition of integrin-mediated cell spreading and migration, and the cellular phosphorylation levels. Conversely, knockdown of endogenous GnT-III expression resulted in increased cell migration, concomitant with an increase in beta1,6 GlcNAc-branched N-glycans on integrins. Thus, N-glycan could be considered as either a positive or negative regulator for biological functions of integrin.
Isaji
Tomoya
T
Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai Miyagi, Japan.
Kariya
Yoshinobu
Y
Xu
Qingsong
Q
Fukuda
Tomohiko
T
Taniguchi
Naoyuki
N
Gu
Jianguo
J
D000117:Acetylglucosamine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000235:genetics; D005821:Genetic Techniques; D006031:Glycosylation; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism
D016023:Integrins; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine