Ciliary length variations impact cilia-mediated signaling and biological responses.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of biochemistry Pub Date : 2024-11-04 DOI:10.1093/jb/mvae057
Yuki Kobayashi, Akie Hamamoto, Yumiko Saito
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Abstract

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.

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纤毛长度的变化会影响纤毛介导的信号传递和生物反应。
初级纤毛是从大多数哺乳动物细胞表面伸出的细如发丝的细胞器。纤毛是一种特化的细胞天线,可因特定刺激而发生很大变化。然而,纤毛长度的变化对细胞信号和行为的影响仍不清楚。因此,我们利用表达纤毛 G 蛋白偶联受体(GPCR)--黑色素浓缩激素(MCH)受体 1(MCHR1)的人视网膜色素上皮 1(hRPE1)细胞,研究了氯化锂(LiCl)、氯化钴(CoCl2)和鱼藤酮等不同化学制剂诱导初级纤毛变长的特征。MCH 主要通过 MCHR1 介导的 Akt 磷酸化诱导纤毛缩短。因此,我们验证了 MCH-MCHR1 轴在纤毛伸长中的正常功能。虽然MCH缩短了氯化锂和鱼藤酮导致的纤毛伸长,但它并没有缩短CoCl2-诱导的纤毛伸长,后者的Akt磷酸化程度较低。此外,还发现血清再添加可延缓 CoCl2 诱导的伸长纤毛的纤毛缩短。相反,鱼藤酮诱导的伸长纤毛通过纤毛顶端的切碎机制迅速缩短。最后,我们发现每种化学物质都对纤毛细胞中纤毛 GPCR 信号转导和血清介导的纤毛结构动态产生了不同的影响。这些结果为理解纤毛长度变化的功能性后果提供了基础。
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来源期刊
Journal of biochemistry
Journal of biochemistry 生物-生化与分子生物学
CiteScore
4.80
自引率
3.70%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Biochemistry founded in 1922 publishes the results of original research in the fields of Biochemistry, Molecular Biology, Cell, and Biotechnology written in English in the form of Regular Papers or Rapid Communications. A Rapid Communication is not a preliminary note, but it is, though brief, a complete and final publication. The materials described in Rapid Communications should not be included in a later paper. The Journal also publishes short reviews (JB Review) and papers solicited by the Editorial Board.
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