Mechanism of Cell Membrane Tension Homeostasis by Membrane Tension Sensor Proteins

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kobe University
• Principal Investigator: Tsujita Kazuya 神戸大学, バイオシグナル総合研究センター, 准教授 (10457054)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 細胞膜の張力 / BARタンパク質 / 光ピンセット

Outline of Final Research Achievements

This study focused on BAR proteins that induce and sense membrane curvature to elucidate the molecular mechanisms by which plasma membrane tension homeostasis is maintained in epithelial cells. Using a combination of optical tweezers and gene knockdown experiments, we identified a BAR protein X that is required for homeostasis of plasma membrane tension. We found that, X, which has a GAP domain for Rac, recruit to the membrane by sensing decreased membrane tension, where it inactive Rac, which in turn activates its competitor, RhoA. This RhoA activation seems to lead to increased membrane tension by increasing membrane-cortex attachment. These results suggest that a feedback regulation between plasma membrane tension and BAR protein X plays an important role in tensional homeostasis of the plasma membrane.

Free Research Field

細胞生物学、生物物理学、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、BARタンパク質が細胞膜張力を制御する仕組みを解明し、細胞膜張力の恒常性維持機構という上皮細胞のintegrityを保つ新しいコンセプトを提示することができた。細胞膜張力の制御・維持機構はよく分かっておらず、本研究成果は、細胞膜の変形を伴う細胞運動、エンドサイトーシス、細胞分裂、極性形成等の動的な生命現象の理解に大きく貢献するものと期待される。また、BARタンパク質Yは浸潤・転移に関わるがん遺伝子としても知られており、Yはがん治療における有望な標的分子となる可能性が考えられる。