Identification of the novel genes which regulated differentiation of neuronal tissues and the diseases caused by their defects
| Project/Area Number |
10470296
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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 |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
SAYA Hideyuki Kumamoto University, School of Medicine, Tumor Genetics & Biology, Professor, 医学部, 教授 (80264282)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Norie Kumamoto University, School of Medicine, Tumor Genetics & Biology, Instructor, 医学部, 助手 (80253722)
NAKAO Mitsuyoshi Kumamoto University, School of Medicine, Tumor Genetics & Biology, Instructor, 医学部, 助手 (00217663)
MIMORI Tatsuyuki Kumamoto University, School of Medicine, Tumor Genetics & Biology, Professor, 医学部, 助教授 (00117384)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1998: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | Drosophila / NE-dlg / p51-nedasin / 1(3)mbt / synapse / calmodulin / EST / Polycomb / DLG / NMDAレセプター / PDZドメイン / p51-nedasin / P-dlg |
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| Research Abstract |
1) NE-dlg is a human homologue of the Drosophila DLG. We found that NE-dlg binds to NMDA receptor subunit 2B at the synaptic membrane sites in neurons, and that their expressions increase in parallel with the onset of a synaptogenesis. NE-dlg was found to interact with PSD-95 in the presence of calmodulin and calcium and is speculated to regulate the clustering of NMDA receptors to form the synapses. Furthermore, we identified a novel cytoplasmic NE-dlg-interacting protein, termed p51-nedasin. We found that nedasin competitively inhibits the binding between the NMDA receptors and NE-dlg. These results suggest that nedasin modifies the dlg-related molecular clustering at the synaptic sites during development of neuronal cells.
2) Recessive mutations of the lethal (3)malignant brain tumor (D-1(3)mbt) gene result in malignant proliferation of the neuroblasts in the Drosophila larval brain. The structure of D-1(3)mbt protein is similar to sex comb on midleg (Scm) protein which is a member of Polycomb group (PcG) proteins. We isolated a human homolog of the 1(3)mbt gene, designated h-1(3)mbt. The h-1(3)mbt is expressed in most of the human normal tissues and cultured cell lines. The h-1(3)mbt protein shows a speckled and scattered distribution in interphase nuclei and localizes to condensed chromosomes in mitotic cells. Overexpression of h-1(3)mbt by a Cre-mediated gene activation system leads to failures of proper chromosome segregation and cytokinesis, which result in formation of multinuclei in U251MG cells. These observations suggest that h-1(3)mbt protein has functions distinct from those of PcG proteins and may play a role in proper progression of cell division.
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Report
(3 results)
Research Products
(31 results)
