1999 Fiscal Year Final Research Report Summary
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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| Keywords | Drosophila / NE-dlg / p51-nedasin / 1(3)mbt / synapse / calmodulin / EST / Polycomb |
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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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Research Products
(19 results)
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[Publications] Nakamura H, Sudo T, Tsuiki H, Miyake H, Morisaka T, Sasaki J, Masuko N, Kochi M, Ushio Y and Saya.H: "Identification of a novel human homolog of the Drosophila dlg, P-dlg, specifically expressed in the gland tissues and interacted with p55."FEBS Letters. 433. 63-67 (1998)
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[Publications] Masuko N, Makino K, Kuwahara H, Fukunaga K, Sudo T, Araki N, Yamamoto H, Yamada Y, Miyamoto E and Saya H: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific MAGUK protein, with calmodulin and PSD-95/SAP90: a possible regulatory role in molecular clustering at synaptic sites"J Biol Chem. 274. 5782-5790 (1999)
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[Publications] Kuwahara H, Araki N, Makino K, Masuko N, Honda S, Kaibuchi K, Fukunaga K, Miyamoto E, Ogawa M and Saya H: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP 102 and NMDA receptor"J Biol Chem. 274. 32204-32214 (1999)
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[Publications] Nishiyama Y, Hirota T, Morisaki T, Hara T, Marumoto T, Iida S, Makino K, Yamamoto H, Hiraoka T, Kitamura N, and Saya H: "A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis"FEBS Letters. 459. 158-165 (1999)
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