Regulation of vascular cell function through control of membrane traffic by cellular lipid signaling

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04673
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Kanazawa University
• Principal Investigator: Takuwa Yoh 金沢大学, 医学系, 教授 (60171592)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: イノシトールリン脂質 / PI3-キナーゼ / スフィンゴ脂質 / スフィンゴシンキナーゼ / 細胞内小胞輸送 / エンドソーム / エンドサイトーシス / シグナル伝達

Outline of Final Research Achievements

We studied the functions of class II phosphoinositide 3-kinase (PI3K) isoforms and their functional difference, by analyzing PI3K-C2α- and PI3K-C2β-knockout (KO) mice. Single KO mice of either gene apparently exhibited normal phenotypes whereas the PI3K-C2α/ PI3K-C2β double KO mice showed abnormalities in two different tissues. We also generated KO mice of the degrading enzyme, PI3Pase, of the class II PI3K product PI-3-P. Tissue-specific homozygous KO mice of PI3Pase showed the similar phenotypes to global KO mice, and the analyses of PI3Pase-deficient cells demonstrated abnormalities in membrane traffic. Homozygous KO mice of sphingolipid metabolizing enzyme, sphingosine kinase, showed exacerbation of vascular lesions. This was mediated by impaired membrane traffic.

Free Research Field

生理学、細胞分子生理学、病態生理学、病態医化学