GM2 Ganglioside Regulates the Function of Ciliary Neurotrophic Factor Receptor in Murine Immortalized Motor Neuron-Like Cells (NSC-34) |
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Authors: | Usuki Seigou Ren Jin Utsunomiya Iku Cashman Neil R Inokuchi Jin-ichi Miyatake Tadashi |
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Institution: | (1) Tokyo Research Institute, Seikagaku Corporation, Tokyo, Japan;(2) Department of Neuroscience, Showa Pharmaceutical University, Tokyo, Japan;(3) Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada;(4) Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan |
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Abstract: | We previously reported that ciliary neurotrophic factor (CNTF) increased the serum-free cell survival of immortalized motor neuron-like cells (NSC-34), and addition of the exogenous ganglioside GalNAc4(Neu5Ac3)Gal4GlcCer (GM2) facilitated cell survival together with CNTF. Moreover 1,4 N-acetylgalactosaminyltransferase (GM2 synthase) activity increased in NSC-34 cells cultured with CNTF. We now have examined whether CNTF-induced cell survival is associated with the collaboration between GM2 and the CNTF receptor (CNTF-R). Despite the presence of CNTF (50 ng/ml), anti-CNTF-R antibody caused cell death and prevented the up-regulation of GM2 synthase expression. The addition of GM2 (1 to 20 M) abrogated the anti-CNTF-R antibody effect which shortened cell survival and blocked GM2 synthase activation. Use of 125I]CNTF showed the specificity of CNTF binding in NSC-34 cells in situ. GM2 produced a 5-fold increase in the CNTF binding affinity per cell but did not change the binding site number. The study by metabolic labeling with 1–14C]N-acetyl-D-galactosamine (14C]GalNAc) showed that biosynthesized GM2 was involved in the immunoprecipitation of CNTF-R. These findings indicate that up-regulated GM2 synthesis induces functional conversion of CNTF-R to the activated state, in which it has affinity for CNTF. We conclude that GM2 is a bio-regulating molecule of CNTF-R in motor neurons. |
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Keywords: | CNTF receptor GM2 motor neuron 1" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0"> 1 4 N-acetylgalactosaminyltransferase neuronal cell death |
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