多纤毛细胞纤毛精确组装的调控机制

高等动物体内气管、脑室管膜及输卵管等上皮组织具有一类富含运动纤毛的多纤毛细胞,通过其细胞表面运动纤毛的周期性摆动可以清洁气管、驱动脑脊液流动和受精卵运动。运动纤毛发生或功能的异常则可导致气管炎、脑积水、不孕不育等多种遗传疾病。然而,在多纤毛细胞分化过程中关于如何精确组装运动性纤毛复杂结构的分子机制仍不清楚。该研究运用蛋白组学、超高分辨率显微成像和电镜等多种技术,发现多纤毛细胞特有的亚细胞结构–纤维状颗粒物是由中心体周围基质蛋白Pcm1相分离形成的具有液体特征的无膜细胞器,不仅参与调控多纤毛细胞摇篮体的组装和空间分布,而且在其多孔状结构中大量富集了特定的基体和纤毛的结构蛋白质,并精确调控这些组分在运动纤毛发生的不同阶段定位到基体和纤毛中,阐明了纤维状颗粒物作为组织者精确调控运动纤毛组装的分子机制。

The Regulatory Mechanism for Accurate Construction of Motile Cilia in Multiciliated Cells

Motile cilia are present on the epithelial surface in large numbers to generate a directional fluid flow that is crucial for various biological processes,such as mucociliary clearance in airways,cerebrospinal fluid circulation in the brain,and fertility.Dysfunction of these cilia causes chronic tracheitis,hydrocephalus and infertility.In spite of the important role of motile cilia,little is known about the mechanism for accurate construction of intricate motile ciliary structures.Here,using a combination of proteomic analysis,super resolution microscopy,electron microscopy and live cell imaging,this article discovers that Pcm1 may undergo phase separation to form FGMs(fibrogranular materials),which regulate deuterosome size,number,and distribution,and selectively concentrate multiple important centriole-related proteins as clients.Disruption of FGMs markedly affects the ultrastructure of motile cilia.Together,these findings demonstrate that FGMs organize deuterosomes and centriole-related proteins to facilitate the faithful assembly of basal bodies and multiciliary axonemes.