β1,4-N-Acetylglucosaminyltransferase III potentiates β1 integrin-mediated neuritogenesis induced by serum deprivation in Neuro2a cells

Abstract

Aspects of the biological significance of the bisecting N-acetylglucosamine (GlcNAc) structure on N-glycans introduced by β1,4-N-acetylglucosaminyltransferase III (GnT-III) in Neuro2a cell differentiation are demonstrated. The overexpression of GnT-III in the cells led to the induction of axon-like processes with numerous neurites and swellings, in which β1 integrin was localized, under conditions of serum starvation. This enhancement in neuritogenesis was suppressed by either the addition of a bisecting GlcNAc-containing N-glycan or erythroagglutinating phytohemagglutinin (E 4-PHA), which preferentially recognizes the bisecting GlcNAc. GnT-III-promoted neuritogenesis was also significantly perturbed by treatment with a functional blocking anti-β1 integrin antibody. In fact, β1 integrin was found to be one of the target proteins of GnT-III, as confirmed by a pull-down assay with E 4-PHA. These data suggest that N-glycans with a bisecting GlcNAc on target molecules, such as β1 integrin, play important roles in the regulation of neuritogenesis. © 2006 Oxford University Press.