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首页> 外文期刊>The FEBS journal >From cell surface to signalling and back: the life of the mammalian FSH receptor
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From cell surface to signalling and back: the life of the mammalian FSH receptor

机译：从细胞表面到信号和背部：哺乳动物FSH受体的寿命

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Follicle-stimulating hormone receptor (FSHR) is a class A G protein-coupled receptor that belongs to the subfamily of glycoprotein hormone receptors (GPHRs). The interaction of FSH with FSHR triggers downstream signaling pathways that play a central role in mammalian reproduction, such as folliculogenesis in females and the maintenance of spermatogenesis in males. This warrants a detailed investigation into FSHR, from its genesis, to the post-translational modifications that enable it to become functionally competent, followed by its trafficking to the cell membrane. Subsequently, FSH-stimulated G(s) uncoupling and transduction of G protein-mediated signaling pathways takes place, after which the receptor undergoes beta-arrestin-mediated internalization and may trigger other noncanonical signaling pathways. The majority of the FSH-FSHR complexes are recycled back to the cell surface and only a small proportion are routed to lysosomal degradation pathways, thus completing the lifecycle of the FSH receptor. Information about important epitopes and aspects of FSH receptor function has been gleaned from a number of sources, including structure-function studies on both naturally occurring and induced mutations, single nucleotide polymorphisms, peptides and antipeptide antibodies corresponding to predicted functional residues, X-ray crystallography analysis and high resolution imaging studies, in addition to the information available for the other GPHRs. In this review, we have traversed through the life cycle of the FSH receptor and discuss the reproductive pathophysiologies that could result from an impairment in receptor function, as may arise from defects during its journey from its birth to its degradation. Moreover, the unresolved questions and challenges that require exploration have been highlighted.
机译：促卵泡激素受体（FSHR）是糖蛋白激素受体（GPHR）亚家族中的一类G蛋白偶联受体。FSH与FSHR的相互作用触发下游信号通路，这些通路在哺乳动物生殖中起着核心作用，例如雌性卵泡发育和雄性精子发育的维持。这就需要对FSHR进行详细的研究，从它的起源到翻译后的修饰，使其具备功能，然后将其运输到细胞膜。随后，FSH刺激G（s）解偶联并转导G蛋白介导的信号通路，之后受体经历β-阻遏素介导的内化，并可能触发其他非经典信号通路。大多数FSH-FSHR复合物被回收到细胞表面，只有一小部分被输送到溶酶体降解途径，从而完成FSH受体的生命周期。有关FSH受体功能的重要表位和方面的信息已从多个来源收集，包括自然发生和诱导突变的结构功能研究、单核苷酸多态性、与预测的功能残基相对应的肽和抗肽抗体、X射线晶体学分析和高分辨率成像研究，除了其他GPHR的可用信息。在这篇综述中，我们回顾了FSH受体的生命周期，并讨论了受体功能受损可能导致的生殖病理生理学，如从其出生到退化的过程中可能出现的缺陷。此外，还强调了需要探索的尚未解决的问题和挑战。

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