Mechanism of degradation and recycling of G protein-coupled receptors by endocytosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06571
• 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: Tokyo University of Science
• Principal Investigator: Toshima Jiro 東京理科大学, 先進工学部生命システム工学科, 教授 (00333831)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: GPCR / エンドサイトーシス / エンドソーム

Outline of Final Research Achievements

G protein-coupled receptors (GPCRs) are the most abundant receptors in human cells and are involved in many physiological phenomena. After being activated by ligand binding, GPCRs are internalized by a cellular function called endocytosis, inactivated, and then degraded or recycled. In this study, we investigated the molecular mechanism by which activated GPCRs are degraded or recycled, using a budding yeast mutants that have defect in the endocytosis of GPCRs, and succeeded to reveal a mechanism for GPCR internalization by the Pan1 protein, and identify the sorting compartment where GPCRs are degraded and recycled. We also revealed a mechanism for Rab5-dependent transport of GPCRs from the sorting compartment to the degradation pathway.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ヒトの細胞には800種を超えるGタンパク質共役型受容体（GPCR）が存在しており、これらの受容体は様々な生理現象に深く関わっている。また、GPCRシグナルの異常はがんをはじめとする多くの疾患を引き起こすことが知られており、このためGPCRは創薬の重要な標的分子であり、実際、市販薬の約4割はGPCRに作用するものである。本研究では、これまで知られていなかったGPCRの不活性化機構を明らかにするこに成功しており、本研究成果は新しいGPCR作用薬の開発の基礎となることが期待できる。