Ciliary length variations impact cilia-mediated signaling and biological responses

Kobayashi Yuki

Hamamoto Akie

Saito Yumiko

The Journal of Biochemistry

Primary cilia are thin hair-like organelles that protrude from the surface of most mammalian cells. They act as specialized cell antennas that can vary widely in response to specific stimuli. However, the effect of changes in cilia length on cellular signaling and behavior remains unclear. Therefore, we aimed to characterize the elongated primary cilia induced by different chemical agents, lithium chloride (LiCl), cobalt chloride (CoCl2) and rotenone, using human retinal pigmented epithelial 1 (hRPE1) cells expressing ciliary G protein-coupled receptor (GPCR), melanin-concentrating hormone (MCH) receptor 1 (MCHR1). MCH induces cilia shortening mainly via MCHR1-mediated Akt phosphorylation. Therefore, we verified the proper functioning of the MCH-MCHR1 axis in elongated cilia. Although MCH shortened cilia that were elongated by LiCl and rotenone, it did not shorten CoCl2-induced elongated cilia, which exhibited lesser Akt phosphorylation. Furthermore, serum readdition was found to delay cilia shortening in CoCl2-induced elongated cilia. In contrast, rotenone-induced elongated cilia rapidly shortened via a chopping mechanism at the tip of the cilia. Conclusively, we found that each chemical exerted different effects on ciliary GPCR signaling and serum-mediated ciliary structure dynamics in cells with elongated cilia. These results provide a basis for understanding the functional consequences of changes in ciliary length.

Akt pathway

G protein-coupled receptor

hTERT-RPE1 cells

melanin-concentrating hormone

primary cilia

eng

Oxford

This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Biochemistry following peer review. The version of record The Journal of Biochemistry, Volume 176, Issue 5, November 2024, Pages 369–383 is available online at: https://doi.org/10.1093/jb/mvae057.

This is not the published version. Please cite only the published version.

この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。

[DOI] https://doi.org/10.1093/jb/mvae057 isVersionOf

日本学術振興会

Japan Society for the Promotion of Science

[Crossref Funder] https://doi.org/10.13039/501100001691

細胞表面に突き出たアンテナ「一次繊毛」が制御する新たな摂食・情動機構の解明

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

19K06739

日本学術振興会

Japan Society for the Promotion of Science

[Crossref Funder] https://doi.org/10.13039/501100001691

細胞センサー一次繊毛の動的変動とその作用点の解析

Regulation of primary cilia dynamics

22K06297

日本学術振興会

Japan Society for the Promotion of Science

[Crossref Funder] https://doi.org/10.13039/501100001691

1次繊毛上に局在するメラニン凝集ホルモン受容体の機能解析

Functional analysis of a melanin-concentrating hormone receptor that localizes to primary cilia

18K14742