| Project/Area Number |
08458187
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | National Institute for Basic Biology |
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Principal Investigator |
NODA Masaharu Natl. Inst.for Basic Biology ProfessorDiv.of Molecular Neurobiol., 基礎生物学研究所, 教授 (60172798)
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| Co-Investigator(Kenkyū-buntansha) |
SHINTANI Takafumi Natl. Inst.for Basic Biology ProfessorDiv.of Molecular Neurobiol.Research Assoc., 基礎生物学研究所, 助手
MAEDA Nobuaki Natl. Inst.for Basic Biology ProfessorDiv.of Molecular Neurobiol.Assoc.Professor, 基礎生物学研究所, 助教授 (90202308)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | 6B4 proteoglycan / PTP zeta / pleiotrophin / knock-out mice / tyrosine phosphatase |
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| Research Abstract |
(1) Signal transduction of PTPzeta
In order to reveal the signal transduction mechanism of PTPzeta, we tried to identify the extracellular ligand and intracellular substrate molecules.We found that heparin-binding growth factors, pleiotrophin (PTN) and midkine (MK), bind to the extracellular domain of PTPzeta.We found that PTPzeta on neurons acts as a receptor for PTN and MK in neurite outgrowth and neuronal migration induced by MK and PTN.We also tried to identify the molecules that bind to the intracellular domain of PTPzeta by using yeast two-hybrid system.We found that some of the PSD-95 family proteins bind to the C-terminal region of PTPzeta, suggesting that this molecule in involved in the synapse formation and plasticity.
(2) Analysis of PTPzeta-targeted mice
We generated mice, in which the PTPzeta gene was replaced by the LacZETA gene by gene targeting.Analysis of LacZETA expression in heterozygous mice indicated that many neurons including pyramidal cells in neocortex and granule cells in dentate gyrus as well as astrocytes produce PTPzeta.We are now studying phenotype of homozygous PTPzeta-targeted mice by using physiological, histochemical and ethological methods, and several abnormalities were found.
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