Study on the regulatory roles of primary cilia relating to feeding and mood control

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06739
• 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: Saito Yumiko 広島大学, 統合生命科学研究科(総), 教授 (00215568)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Gタンパク質共役型受容体 / 一次繊毛 / 摂食 / 海馬 / RNAseq / アクチン結合タンパク質 / ベータアミロイド / 情動

Outline of Final Research Achievements

The primary cilium is a plasma membrane-protruding sensory organelle that efficiently conveys signaling cascades in a highly ordered microenvironment. Its signaling is mediated, in part, by a limited set of GPCRs preferentially enriched in the cilium membrane. This includes melanin-concentrating hormone (MCH) receptor 1 (MCHR1), which plays a role in feeding and mood.　By extensive biological and pharmacological studies of ciliary MCHR1, I have accomplished that (1) Discovery of the biological phenomenon “cilia length shortening via ciliary MCHR1” in MCHR1-expresing RPE1 cell and CA1 hippocampal neurons in vitro and in vivo (the starved state mice), (2) Identification of novel and important regulatory step underlying cilia length control via ciliary MCHR1, (3) Finding of impairment of ciliary dynamics in an APP knock-in mouse model of Alzheimer’s disease. Further, Aβ is found to reduce cilia length in cultured hippocampal neuron.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、肥満動物の繊毛縮退に繋がる可能性を持つ「繊毛縮退モデル系群（ヒトiPSを含む）」に加え、鋭敏なvivo検出系も完成することができた。さらに、繊毛発のMCHR1シグナリングリレー経路の存在も明らかにした。これらの結果は、これまでの細胞膜発現系を用いたGPCR研究では得られなかったものである。従って、神経突起やシナプスが主眼ではなく、非シナプス性小器官である1次繊毛からアプローチを行うことで、摂食情動に対する新たな治療薬の開発につながる可能性がある。