Elucidation of molecular mechanis of primaly cilia regulation via extracellular stiffness.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15363
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Yamaguchi University
• Principal Investigator: TOKUNAGA Masayuki 山口大学, 大学院医学系研究科, 助教 (10845043)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: YAP / ARHGAP11A / 硬さ / １次繊毛

Outline of Final Research Achievements

Extracellular mechanical stimuli regulate cell growth and differentiation, while cells maintain an appropriate extracellular environment; YAP play a central role in this homeostatic mechanism and therefore YAP mechanohomeostasis has been proposed. However, the detail mechanisms of how extracellular mechanical stimuli are transmitted to YAP are still unclear. It has been shown that YAP and ARHGAP11A form negative feedback. However, the mechanisms regulating the subcellular localisation of ARHGAP11A remain unclear. In this study, I show that ARHGAP11A negatively regulates YAP via the Hippo pathway and mechanosensing primary cilia by sensing the stiffness of the extracellular environment and altering its subcellular localisation.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、細胞外環境の硬さによるARHGAP11Aを介したYAPの制御機構の一端を解明しようとするものである。がん組織において、組織が硬くなることはよく知られているが組織の硬さとがんの悪性化には不明な点が多い。本研究により細胞外環境によるYAPの制御機構が解明できれば、新たながん治療の標的になりうるため、社会的意義は大きい。