Regulation of cellular function by late endosomal kinase signaling

2014 Fiscal Year Final Research Report

• Project/Area Number: 23370087
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Osaka University
• Principal Investigator: NADA Shigeyuki 大阪大学, 微生物病研究所, 准教授 (50291448)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Tohru 北里大学, 理学部, 教授 (50280962)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: リソソーム / メンブレントラフィック / 細胞内情報伝達

Outline of Final Research Achievements

A membrane-anchoring protein p18, which is localizing onto late endosomes and lysosomes, takes roles to regulate cell growth and intracellular membrane trafficking. Here, the kinase signal pathways interacting with p18 were analyzed and we found that mTORC1 and its downstream effects including the change of gene expression is the major path of membrane trafficking regulation. As to the cell growth control, we found that mTORC2 is activated by the suppression of mTORC1 in p18 knockout cells, and activated mTORC2 induces the expression of cell cycle inhibitor proteins through the SGK1-FoxO3a axis. To access the physiological importance of p18 in vivo, a keratinocyte-specific conditional p18 knockout mouse was generated, and we found that p18 act as an essential regulator for keratinocyte differentiation and epidermal barrier formation. These results indicate that p18 and associated kinase signals are crucial for tissue formation and the regulation of cellular function.

Free Research Field

細胞生物学