Functional analysis of NPY2R and 5R in primary cilia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06249
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Hiroshima University
• Principal Investigator: Kobayashi Yuki 広島大学, 統合生命科学研究科(総), 特定准教授 (80736421)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 一次繊毛 / GPCR / NPYR

Outline of Final Research Achievements

The primary cilium, an organelle that most cells possess only one cilium, has been forgotten for nearly 100 years because of its immobility. Recently, several G protein-coupled receptors (GPCRs) have been reported to localize on the primary ciliary membrane rather than on the plasma membrane. Since the primary cilia are physically separated from the cytoplasm, it is possible that the primary cilia-specific behavior of GPCRs (intracellular signaling) occurs in the primary cilia. In this application, we focused on neuropeptide Y (NPY) receptors involved in feeding. We found that NPY2R and NPY5R are expressed specifically in primary cilia, and that they shorten primary cilia in response to NPY. In addition, they found that the same phenomenon occurs in vivo.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

これまで生命現象の根幹を担う細胞内シグナルの解析は、細胞膜上に発現した受容体を介して研究が進められてきた。これは、培養細胞作出の過程でほとんどの細胞の一次繊毛が退化してしまうことに起因する。そこで申請者は、一次繊毛局在型GPCRの生理機能を真に解明するためには、「一次繊毛という特異なオルガネラに局在する受容体の特徴的なシグナル経路」を明らかにすることの重要性を提唱してきた。本申請は強力な摂食亢進作用を有するNPY受容体に着目したものであり、本来の発現場所である一次繊毛における挙動を詳細に解析した。本研究成果は肥満を含む現代病の新規創薬等の橋頭保となりえる基礎研究である。