2003 Fiscal Year Final Research Report Summary
Binding of soluble myelin associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction
| Project/Area Number |
14570590
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
YASUDA Hitomi Shiga University of Medical Science Third Department of Medicine, Assistant Professor, 医学部, 講師 (80135467)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAI Hiromichi Shiga University of Medical Science Third Department of Medicine, Senior resident, 医学部, 医員
MAEDA Kengo Shiga University of Medical Science Third Department of Medicine, Instructor, 医学部, 助手 (80324581)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Ganglioside knockout mice / cerebellar granular cells / Inhibition of neurite outgrowth / MAG / Nogo, / RhoA / Lipid raft / p75NTR |
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| Research Abstract |
Myelin-assocoated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. The binding partner for membrane-bound form of MAG is shown to be the Nogo receptor. Here we show that gangliosides, GT1b and GD1a, are functional binding partners for soluble MAG-Fc. Postnatal cerebellar neurons from mice deficient in the GalNacT gene are insensitive to MAG with regard to neurite outgrowth and lack in the activation of RhoA. MAG-Fc or the antibody to GT1b and GD1a elicites recruitment of p75NTR to lipid rafts, specialized microdomain for signal transduction. Disruption of lipid rafts results in abolishment of inhibitory effect of MAG-Fc as well as the Nogo peptide. These findings establish gangliosides as functional binding partner for soluble MAG. Gangliosides may play a role in translocation of p75 NTR to lipid rafts for initiation of the signal transduction.
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