The etiological mechanism of developmental disorder derived from deregulation of centrosomal proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06147
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Ehime University (2023); The University of Tokyo (2021-2022)
• Principal Investigator: Nakamura Takanori 愛媛大学, プロテオサイエンスセンター, 講師 (30707576)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 中心体蛋白質 / 個体発生 / 初期発生 / 発育不全 / 小頭症 / 中心体複製 / がん / 染色体不安定性

Outline of Final Research Achievements

Centrosomes, an intracellular organelle, play a pivotal role in mitotic spindle formation and subsequent chromosome segregation, as well as the formation of organs and tissues. The structural or functional aberration of centrosomes causes various diseases such as tumorigenesis, ciliopathy, and male infertility. However, since the molecular mechanism underlying centrosome duplication and ciliogenesis has not been fully understood, the pathological mechanism, induced by centrosomal aberration, of tumorigenesis, growth failure and male infertility, has not been also illy defined. We therefore aimed to elucidate the mechanism of how centrosomal dysfunction caused by genetic mutations drives growth failure. We then found a pathological mechanism underlying growth failure induced by missense mutation of centrosomal proteins.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

中心体を構成するタンパク質の機能的あるいは構造的な異常は発がんリスクを高める要因となるだけでなく、発育不全疾患あるいは男性不妊症などの主要因となる。しかし発育不全疾患は数千人に1人の低頻度で発症する希少疾患であるため、その病態機構の解明に加えて同疾患治療法の確立も現在進展していない。このため中心体の生理機能の解明は発育不全疾患の発症機構の本質的理解に資するだけでなく、疾患治療の分子マーカーあるいは創薬標的分子の創出にも繋がる可能性を秘めている。このため本研究は大きな学術的および社会的意義を持つ。