| Project/Area Number |
11670032
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | National Institute of Neuroscience, NCNP |
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Principal Investigator |
AKAZAWA Chihiro Natl. Inst. Neuroscience, National Center of Neurology and Psychiatry, Head, 神経研究所, 室長 (80291160)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | GDNF / GFRα-1 / c-Ret / Neuronal regeneration / skeletal muscle / Facial nerve / Motor neuron / Neurotrophic factor / 筋疾患 / 運動ニューロン |
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| Research Abstract |
A variety of neurotrophic factors have been characterized for promoting motor neuron survival. As one of the target-derived trophic factors, glial cell line-derived neurotrophic factor (GDNF) has been shown to exert its effects on motor neurons via a receptor complex including GDNF receptor alpha 1 (GFRα-1) and c-Ret. The c-Ret receptor tyrosine kinase is an essential component of the GDNF ligand family that consists of glial cell line-derived neurotrophic factor, neurturin, persephin, and artemin. Although c-Ret cannot bind GDNF by itself, it transduces signaling in a complex with GFRα-1 (GDNF receptor alpha-1), a glycosyl phosphatidylinositol (GPI)-anchored protein that binds GDNF with high affinity. Thus, the ligand binding and transmembrane signaling are regarded to be specified for GFRα-1 and c-Ret, respectively. Axotomy of facial nerve induced up-regulation of GFRα-1 and c-Ret mRNAs in adult rats. The local administration of GDNF at the site of axotomy resotred up-regulation of GFRα-1 mRNA but not c-Ret. This result indicates that the mechanism of GDNF receptor up-regulation may differ between GFRα-1 and c-Ret.
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