Liu Peiwei, Liu Ying, Zhou Jun
Shandong Provincial Key Laboratory of Animal Resistance Biology , College of Life Sciences in Shandong Normal University, Jinan 250358, China.
College of Life Sciences, Nankai University, Tianjin 300071, China.
J Cell Sci. 2023 Feb 1;136(3). doi: 10.1242/jcs.260565. Epub 2023 Feb 8.
Cilia are surface-exposed organelles that provide motility and sensory functions for cells, and it is widely believed that mechanosensation can be mediated through cilia. Polycystin-1 and -2 (PC-1 and PC-2, respectively) are transmembrane proteins that can localize to cilia; however, the molecular mechanisms by which polycystins contribute to mechanosensation are still controversial. Studies detail two prevailing models for the molecular roles of polycystins on cilia; one stresses the mechanosensation capabilities and the other unveils their ligand-receptor nature. The discovery that polycystins interact with mastigonemes, the 'hair-like' protrusions of flagella, is a novel finding in identifying the interactors of polycystins in cilia. While the functions of polycystins proposed by both models may coexist in cilia, it is hoped that a precise understanding of the mechanism of action of polycystins can be achieved by uncovering their distribution and interacting factors inside cilia. This will hopefully provide a satisfying answer to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD), which is caused by mutations in PC-1 and PC-2. In this Review, we discuss the characteristics of polycystins in the context of cilia and summarize the functions of mastigonemes in unicellular ciliates. Finally, we compare flagella and molecular features of PC-2 between unicellular and multicellular organisms, with the aim of providing new insights into the ciliary roles of polycystins in general.
纤毛是细胞表面暴露的细胞器,为细胞提供运动和感觉功能,人们普遍认为机械感觉可通过纤毛介导。多囊蛋白-1和-2(分别为PC-1和PC-2)是可定位于纤毛的跨膜蛋白;然而,多囊蛋白促成机械感觉的分子机制仍存在争议。研究详细阐述了关于多囊蛋白在纤毛上分子作用的两种主流模型;一种强调机械感觉能力,另一种揭示其配体-受体性质。多囊蛋白与鞭毛的“毛发状”突出物鞭毛茸相互作用这一发现,是在确定纤毛中多囊蛋白相互作用分子方面的一项新发现。虽然两种模型提出的多囊蛋白功能可能在纤毛中共存,但希望通过揭示它们在纤毛内的分布和相互作用因子,能够精确了解多囊蛋白的作用机制。这有望为常染色体显性多囊肾病(ADPKD,由PC-1和PC-2突变引起)的发病机制提供令人满意的答案。在本综述中,我们在纤毛的背景下讨论多囊蛋白的特征,并总结鞭毛茸在单细胞纤毛虫中的功能。最后,我们比较单细胞和多细胞生物中鞭毛和PC-2的分子特征,旨在为多囊蛋白在纤毛中的作用提供新的见解。