2001 Fiscal Year Final Research Report Summary
Genetic identification ofa gene encoding a proteinase that digests Notch and β-amyloid precursor protein
| Project/Area Number |
12680703
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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 |
Cell biology
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
KENJI Matsuno Faculty of Industrial Science andTechnology, Associate Professor, 基礎工学部, 助教授 (60318227)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Notch / β-amyloid / Alzheimer's deaease / Presenilin / Drosophila / Genetic screen / proteinase / Cell signaling |
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| Research Abstract |
Local cell-cell interactions are essential for the development of multicellular organisms. Notch signaling is involved in cell-cell communications that regulate a broad spectrum of cell-fate determinations in organisms ranging from the fly to mammals.
In Drpfophila, Notch encodes a 300-kDa single-pass transmembrane receptor. There are strong evidences supporting the idea that the ligand-dependent activation of Notch induces proteolytic cleavage of Notch itself, so that the intracellular domain of Notch is released from the cell mdmbrane and moves to the nucleus. This cleavage was shown to depend on the function of Presenilin and a γ-secretase-like proteinase. It has been known that Presenilin and the γ-secretase-like proteinase also cleave β-Amyloid precursor protein (β-APP) to generate the pathogenic β-Amyloid polypeptides. Namely, it suggests that Notch and β-APP are common substrates for and the γ-secretase-like p roteinase.
In this study, we screened genes that were essential for Notch signaling, because they may encode the γ-secretase-like proteinase or a protein essential for a function of the γ-secretase-like proteinase. . We found a mutant, named as neurotic, is a novel maternal neurogenic gene. In all organs tested, the function of neurotic is essential for Notch signaling, neurotic interacted genetically with mutations of the genes involved in Notch signaling. We identified a genomic region that contains neurotic locus as a single transcription unit. Currently, the function of neurotic in Notch signaling is investigated.
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[Publications] Matsuno. K., Ito, M., Hori, K., Miyashita, R, Suzuki, S., Kishi, N., Artavanis-Tsakonas, S. and Okano, H. Yamamoto N., Yamamoto Si S., Inagaki R,: "Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling."Development. (in press). (2001)
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[Publications] Kitagawa, M., Oyama, T., Kawashima, T., Yedvobnic, B., Matsuno. K. and Harigaya, K: "Mastermind coordinates the nuclear form of Notch and a CSL protein to bind a transcriptional activator complex on target promoters,"Mol.Cell.Biol.. 13. 4337-4346 (2001)
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[Publications] Kishi, N., Tang, Z., Maeda, Y, Hirai, A., Mo, R., Ito, M., Suzuki, S., Kakao, K., Kinoshita, T., Kadesch, T., Hui, C.-c., ArtavanisTsakonas, S., Okano, H. and Matsuno. K.: "Murin homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis."Int. J. Dev. Neurosci.. 19. 21-35 (2001)
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