Global analysis of G-protein-coupled receptor signaling by fluorescent GPCR ligand

2015 Fiscal Year Final Research Report

• Project/Area Number: 25440054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: Toshima Jiro 東京理科大学, 基礎工学部, 准教授 (00333831)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: GPCR / エンドサイトーシス / 小胞輸送 / Rab5 / 小胞輸送

Outline of Final Research Achievements

G protein-coupled receptors (GPCRs) are heptahelical membrane proteins that comprise one of the largest families of cell surface signaling receptors in the human genome. GPCRs are the targets of ~30% of the drugs currently used for the treatment of a wide range of human diseases. Thus, elucidating the mechanism of regulation of GPCR signaling is essential for the development of more effective and safer therapeutic agents. Endocytic internalization of G protein-coupled receptors (GPCRs) plays a critical role in down-regulation of GPCR signaling. In this study, we screened for yeast single-gene deletion mutants exhibiting defects in GPCR endocytosis. By using fluorescent endocytic cargo, we identified 195 mutants that exhibited delay in endocytic transport of GPCR. Among these genes, we focused on yeast Rab5, Vps21p. We found that yeast Rab5 mutant shows significant delay of GPCR transport to the vacuole. We also found a novel endocytic pathway mediated by the AP-3 complex.

Free Research Field

細胞生物学