Functions of regulators for Notch signaling, almondex/TM2D3

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08577
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: International University of Health and Welfare (2017-2019); Chiba University (2016)
• Principal Investigator: Motoo Kitagawa 国際医療福祉大学, 医学部, 教授 (40262026)
• Co-Investigator(Kenkyū-buntansha): 増田 渉 埼玉医科大学, 医学部, 助教 (00623464)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: Notchシグナル / TM2D3 / almondex

Outline of Final Research Achievements

We have examined mouse Tm2d3 and its Drosophila homolog almondex (amx) by using their respective deficient mutant animals.
Murine Tm2d3-deficient cultured cells were found to have decreased surface expression of both Notch1 and Notch2 as compared with the wild type cells. In the ventral presumptive mesodermal cells of early Drosophila embryos, Notch and its ligand Delta interact, are endocytosed, and co-localize in intracellular vesicles. In contrast, such vesicles were scarcely observed in the amx-deficient mutants.
Based on these results, it is concluded that TM2D3/amx positively regulates surface expression of Notch receptors to interact with their ligands.

Free Research Field

細胞シグナル伝達機構の生化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまで不明であったTM2D3とalmondexの生化学的、細胞生物学的な機能を初めて明らかにしたものである。Notchシグナルの異常は各種悪性腫瘍、遺伝性疾患の原因であることが知られているが、本研究の成果によって今後こうした問題の理解が深まり、さらに解決の手がかりが得られることを期待する。またヒトにおいて、TM2D3のある遺伝子多型が晩期発症型アルツハイマー病の発症危険率を約7.5倍上昇させ、さらに発症年齢を約10年早めることが知られているが、本研究の成果が今後この機構を解明するために役立つことも期待する。