Sensing mechanism and signal output of plasma membrane lipid asymmetry

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06561
• 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: Nagoya University
• Principal Investigator: Obara Keisuke 名古屋大学, 理学研究科, 講師 (30419858)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Plasma membrane / lipid / lipid asymmetry / yeast

Outline of Final Research Achievements

We investigated into the mechanism of lipid asymmetry sensing by the sensor protein Rim21 and how activated Rim21 evokes signal transduction pathway. As a result, we suggested that some charged amino acid residues within and near the "sensor motif" which is located in the C-terminal cytosolic region of Rim21 (Rim21C) play pivotal roles in interaction between the plasma membrane inner leaflet and Rim21C. This is a great progress that may open the door for elucidation of molecular mechanism underlying lipid asymmetry sensing.
We also found that alterations in some physicochemical variants outside the cell, e.g. pH and salt concentration, may affect the state of lipid asymmetry. Of them at least pH elevation and high salt stress, was found to be sensed by Rim21 through alterations in lipid asymmetry. This finding deserves attention in that it sheds light on a novel aspect of the plasma membrane as a sensor structure for physicochemical variants.

Free Research Field

Cell Biology

Academic Significance and Societal Importance of the Research Achievements

細胞膜脂質非対称の調節は、細胞の生存に必須な基本的な性質であるにも関わらず、その状態がどの様にモニターされているかは未知のままである。本研究は、その様な細胞の基本機能の一端を明らかにする点で重要である。また、Rim21の様な多重膜貫通タンパク質が可溶性領域を触角の様に用いて膜表面の状態をモニターする例は知られておらず、本研究は「タンパク質ー生体膜相互作用」の新たなパラダイムとなり得る。
細胞膜が、細胞外物理化学変数の変化に対して巨大なセンサーとして働き、脂質非対称などの状態変化を通して各種センサータンパク質群に提示することを示唆し、細胞膜の役割そのものに新たな一面が加わる可能性を示した。