Relationship between architecture and function of intraciliary protein trafficking complex: molecular basis for ciliopathies

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H00980
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Nakayama Kazuhisa 京都大学, 薬学研究科, 教授 (40192679)
• Co-Investigator(Kenkyū-buntansha): 申 惠媛 京都大学, 薬学研究科, 准教授 (10345598) ; 加藤 洋平 京都大学, 薬学研究科, 連携教授 (90568172) ; 原田 彰宏 大阪大学, 大学院医学系研究科, 教授 (40251441)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 繊毛 / 繊毛病 / タンパク質輸送 / タンパク質複合体

Outline of Final Research Achievements

Primary cilia serve as cellular antennae. Defects in intraflagellar transport (IFT) machinery cause the ciliopathies with a variety of severe symptoms. In this study, we identified aberrant protein-protein interactions and abnormalities at the level of ciliary function, which had been a black box between ciliopathy-causing gene mutations (genotypes) and abnormal phenotypes at the individual level (symptoms). In particular, with regard to ciliopathies caused by mutations in protein complexes and motor proteins that mediate IFT, we were able to link these protein-level mutations to abnormalities in protein-protein interactions and at the level of cilia, thus clarifying the molecular basis of ciliopathies.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、一部の繊毛病に関して、その発症の分子基盤を明らかにできた。今後は同様の手法を用いて他の繊毛病についても、基盤の解明にもつなげることができる。現在は治療法のない繊毛病ではあるが、地道に発症機構を解明していけば、将来的には早期介入などの治療法の開発につながる可能性があることを示したことは、本研究の学術的意義である。