An inhibitory effect of cholesterol on expressing eat me signals in human erythrocyte membrane

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Takakuwa Yuichi 東京女子医科大学, 医学部, 教授 (40113740)
• Co-Investigator(Kenkyū-buntansha): MANNO Sumie 東京女子医科大学, 医学部, 講師 (10101205) ; SAITO Masaki 東京女子医科大学, 医学部, 助教 (50400271) ; KOSHINO Ichiro 東京女子医科大学, 医学部, 講師 (80328377) ; TANAKA Shotaro 東京女子医科大学, 医学部, 助教 (90380667) ; ARASHIKI Nobuto 東京女子医科大学, 医学部, 助教 (80569658)
• Research Collaborator: Mohandas Narla New York Blood Center, Red Cell Physiology Laboratory
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: リン脂質非対称性 / フォスファチジルセリン / Eat me signal / ヒト赤血球膜 / コレステロール / スクランブラーゼ / フリッパーゼ

Outline of Final Research Achievements

In the lipid bilayer of human erythrocyte membranes, asymmetric distribution of phospholipids, especially phosphatidylserine in the inner leaflet, is essential for erythrocyte function and survival as well as in other cells. Although, reputedly, flippase and scramblase are required for the maintenance and disruption of the lipid asymmetry, respectively, responsible molecules and their mechanisms are unclear. This study identified ATP11C as a major flippase and PLSCR1 as a major scramblase and demonstrated an inhibitory effect on PLSCR1-dependent scramblase activity as a novel function of cholesterol which exhibits abundantly in erythrocyte membranes. This finding certified that, contrary to the generally accepted theory, cholesterol inhibition of scrambling activity rather than flipping activity driven by ATP11C contributes to maintaining asymmetric distribution of phospholipids.

Free Research Field

生化学