Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; email:
Annu Rev Physiol. 2023 Feb 10;85:425-448. doi: 10.1146/annurev-physiol-031522-084334.
Polycystin subunits can form hetero- and homotetrameric ion channels in the membranes of various compartments of the cell. Homotetrameric polycystin channels are voltage- and calcium-modulated, whereas heterotetrameric versions are proposed to be ligand- or autoproteolytically regulated. Their importance is underscored by variants associated with autosomal dominant polycystic kidney disease and by vital roles in fertilization and embryonic development. The diversity in polycystin assembly and subcellular distribution allows for a multitude of sensory functions by this class of channels. In this review, we highlight their recent structural and functional characterization, which has provided a molecular blueprint to investigate the conformational changes required for channel opening in response to unique stimuli. We consider each polycystin channel type individually, discussing how they contribute to sensory cell biology, as well as their impact on the physiology of various tissues.
多囊蛋白亚基可以在细胞的各种隔室的膜中形成异型和同型四聚体离子通道。同型四聚体多囊蛋白通道是电压和钙调节的，而异型四聚体版本则被认为是配体或自切调节的。它们的重要性体现在与常染色体显性多囊肾病相关的变体以及在受精和胚胎发育中的重要作用上。多囊蛋白组装和亚细胞分布的多样性使得这一类通道具有多种感觉功能。在这篇综述中，我们强调了它们最近的结构和功能表征，这为研究通道对独特刺激开放所需的构象变化提供了分子蓝图。我们逐个讨论每种多囊蛋白通道类型，讨论它们如何促进感觉细胞生物学，以及它们对各种组织生理学的影响。
