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Analysis of ciliary status via G-protein-coupled receptors localized on primary cilia
Microscopy ( IF 1.5 ) Pub Date : 2020-07-06 , DOI: 10.1093/jmicro/dfaa035
Yuki Kobayashi 1 , Akie Hamamoto 2 , Yumiko Saito 1
Affiliation  

G-protein-coupled receptors (GPCRs) comprise the largest and most diverse cell surface receptor family, with more than 800 known GPCRs identified in the human genome. Binding of an extracellular cue to a GPCR results in intracellular G protein activation, after which a sequence of events can be amplified and optimized by selective binding partners and downstream effectors in spatially discrete cellular environments. Because GPCRs are widely expressed in the body, they help to regulate an incredible range of physiological processes from sensation to growth to hormone responses. Indeed, it is estimated that about 30% of all clinically approved drugs act by binding to GPCRs. The primary cilium is a sensory organelle composed of a microtubule axoneme that extends from the basal body. The ciliary membrane is highly enriched in specific signaling components, allowing the primary cilium to efficiently convey signaling cascades in a highly ordered microenvironment. Recent data demonstrated that a limited number of non-olfactory GPCRs, including somatostatin receptor 3 and melanin-concentrating hormone receptor 1 (MCHR1), are selectively localized to cilia on several mammalian cell types including neuronal cells. Utilizing cilia-specific cell biological and molecular biological approaches, evidence has accumulated to support the biological importance of ciliary GPCR signaling followed by cilia structural changes. Thus, cilia are now considered a unique sensory platform for integration of GPCR signaling toward juxtaposed cytoplasmic structures. Herein we review ciliary GPCRs and focus on a novel role of MCHR1 in ciliary length control that will impact ciliary signaling capacity and neuronal function.

中文翻译:

通过位于初级纤毛上的 G 蛋白偶联受体分析纤毛状态

G 蛋白偶联受体 (GPCR) 包括最大和最多样化的细胞表面受体家族,在人类基因组中鉴定出 800 多种已知的 GPCR。细胞外线索与 GPCR 的结合导致细胞内 G 蛋白激活,之后,在空间离散的细胞环境中,可以通过选择性结合配偶体和下游效应子放大和优化一系列事件。由于 GPCR 在体内广泛表达,它们有助于调节从感觉到生长再到激素反应的一系列令人难以置信的生理过程。事实上,据估计,所有临床批准的药物中约有 30% 通过与 GPCR 结合起作用。初级纤毛是一种感觉细胞器,由从基体延伸的微管轴丝组成。纤毛膜富含特定的信号成分,使初级纤毛能够在高度有序的微环境中有效地传递信号级联。最近的数据表明,包括生长抑素受体 3 和黑色素浓缩激素受体 1 (MCHR1) 在内的有限数量的非嗅觉 GPCR 选择性地定位于包括神经元细胞在内的几种哺乳动物细胞类型的纤毛。利用纤毛特异性细胞生物学和分子生物学方法,已有证据支持纤毛 GPCR 信号传导以及纤毛结构变化的生物学重要性。因此,纤毛现在被认为是将 GPCR 信号整合到并列细胞质结构的独特感觉平台。
更新日期:2020-07-06
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