Abstract
beta-1,4-N-Acetylglucosaminyltransferase III (GnT-III: EC 2.4.1.144) is a pivotal glycosyltransferase which participates in branch formation by catalysis of the synthesis of a bisecting GlcNAc structure in N-glycans. These structures are thought to be one of the unique features of the N-glycans of neural tissues. To examine the intracellullar role of GnT-III expression and its product in neural cells, its gene was overexpressed in rat pheochromocytoma PC12 cells which normally express a low level of GnT-III. In the GnT-III gene-transfected cells, lectin blot analysis showed that some glycoproteins showed increased levels of bisecting GlcNAc structures. Following treatment with nerve growth factor (NGF) the control cells showed neurite outgrowth for differentiation whereas the transfectants showed no morphological response or change in the rate of cell growth. Transient tyrosine phosphorylation of the Trk/NGF receptor was detected at 5-15 min after NGF treatment in control cells, but not detected in the GnT-III gene-transfected cells despite the intact binding of NGF to the cells. Moreover the dimerization of Trk with NGF treatment was not induced in the GnT-III transfectant as compared with the dimerization seen in control cells. These results indicate that overexpression of GnT-III gene in PC12 cells affects some functions of glycoprotein receptors such as Trk by alteration of N-glycan structures, and results in changes in the intracellular signaling pathway of tyrosine phosphorylation modified by NGF.
Highlights
The marked changes in the sugar chain structures of cell surface membrane occurring during ontogenesis and oncogenesis suggest that they play pivotal roles in cell differentiation and proliferation [1]
We have investigated the biological roles of GnTIII expression and its bisecting GlcNAc product in rat pheochromocytoma PC12 cells by introduction of the GnT-III gene
Certain N-glycan structures of glycoproteins appear to play an important role in neural cell development [3, 4]
Summary
The marked changes in the sugar chain structures of cell surface membrane occurring during ontogenesis and oncogenesis suggest that they play pivotal roles in cell differentiation and proliferation [1]. Sultant pathology showed that complex type N-glycans are required for normal embryonic development, especially of neural tissues [3, 4] In such tissues, it is known that the level of polysialyl Nglycans decreases in the neural cell adhesion molecule as these cells mature. The tissue distribution of its mRNA showed that the GnT-III transcript was high in the brain and kidney of the mouse [14] Such high levels for the expression of GnT-III mRNA seem to be compatible with the existence of unique N-glycan structures in brain including bisecting GlcNAc. Several experimental approaches have been used to elucidate the role of GnT-III in cultured cells [15, 16]. We have investigated the biological roles of GnTIII expression and its bisecting GlcNAc product in rat pheochromocytoma PC12 cells by introduction of the GnT-III gene
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