一次繊毛解析に適した数種のGタンパク質共役型受容体の選択と機能解析

• Published in: 日本薬理学会年会要旨集 p. 3-P2-46
• Main Authors: 宮本, 達雄, 斎藤, 祐見子, 西村, 宣哉, 小林, 勇喜, 徳永, 優希
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: feeding; GTP-binding protein (G-protein); neuropeptide; receptor
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_3-P2-46

G-protein-coupled receptors (GPCRs), which constitute a family of highly diverse membrane receptors, are primarily localized in the plasma membrane without an agonist. Unexpectedly, in 2008, a very limited number of GPCRs such as feeding-related melanin-concentrating hormone receptor 1 (MCHR1) was found to be selectively targeted to a sole organelle named the primary cilium on neuronal cell. The ciliary membrane is enriched in specific signaling molecules, allowing the primary cilium as a sensitive signaling hub in a highly ordered microenvironment. A recent localization screening identified more than 20 ciliary GPCRs. At present, MCHR1 is widely recognized as a representative ciliary GPCR, because its localization in the cilium is reproduced in many different laboratories. In order to establish a definitive list of ciliary GPCRs, we cloned 8 GPCRs, transfected them into hRPE1, NIH3T3 and IMCD cells, and characterized its subcellular localization. We confirmed that feeding-associated neuropeptide Y receptor 2 (Y2) and 5 (Y5), and two dopamine receptors are localized to the primary cilia in all cell models. Next, we found that a ligand caused significant cilia shortening in MCHR1-, Y2- and Y5-expressing cells, respectively. Subsequent experiments showed that Gi/o-Akt phosphorylation is involved in the initial stage of ligand-induced cilia shortening via MCHR1 and Y2 but not Y5. Further characterization of these ciliary GPCRs will provide potential molecular mechanisms to link ciliary length control with food intake and energy metabolism.