Cilia Cell Biology, Institute of Molecular Physiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Imaging Core Facility, Cell Biology Unit, University Medical Centre, Johannes Gutenberg University Mainz, 55101 Mainz, Germany.
J Mol Cell Biol. 2023 Aug 3;15(4). doi: 10.1093/jmcb/mjad022.
Primary cilia are microtubule-based cell organelles important for cellular communication. Since they are involved in the regulation of numerous signalling pathways, defects in cilia development or function are associated with genetic disorders, collectively called ciliopathies. Besides their ciliary functions, recent research has shown that several ciliary proteins are involved in the coordination of the actin cytoskeleton. Although ciliary and actin phenotypes are related, the exact nature of their interconnection remains incompletely understood. Here, we show that the protein BBS6, associated with the ciliopathy Bardet-Biedl syndrome, cooperates with the actin-bundling protein Fascin-1 in regulating filopodia and ciliary signalling. We found that loss of Bbs6 affects filopodia length potentially via attenuated interaction with Fascin-1. Conversely, loss of Fascin-1 leads to a ciliary phenotype, subsequently affecting ciliary Wnt signalling, possibly in collaboration with BBS6. Our data shed light on how ciliary proteins are involved in actin regulations and provide new insight into the involvement of the actin regulator Fascin-1 in ciliogenesis and cilia-associated signalling. Advancing our knowledge of the complex regulations between primary cilia and actin dynamics is important to understand the pathogenic consequences of ciliopathies.
原发性纤毛是一种重要的细胞细胞器，由微管组成，在细胞通讯中发挥作用。由于它们参与了众多信号通路的调节，纤毛发育或功能的缺陷与遗传疾病有关，统称为纤毛病。除了它们的纤毛功能外，最近的研究表明，几种纤毛蛋白参与了肌动蛋白细胞骨架的协调。尽管纤毛和肌动蛋白表型相关，但它们之间的确切联系仍不完全清楚。在这里，我们表明与纤毛病 Bardet-Biedl 综合征相关的蛋白 BBS6 与肌动蛋白束蛋白 Fascin-1 合作调节丝状伪足和纤毛信号。我们发现 Bbs6 的缺失可能会通过与 Fascin-1 的相互作用减弱而影响丝状伪足的长度。相反，Fascin-1 的缺失会导致纤毛表型，随后影响纤毛 Wnt 信号，可能与 BBS6 合作。我们的数据阐明了纤毛蛋白如何参与肌动蛋白的调节，并为肌动蛋白调节因子 Fascin-1 参与纤毛发生和纤毛相关信号提供了新的见解。深入了解原发性纤毛和肌动蛋白动力学之间的复杂调节对于理解纤毛病的发病机制具有重要意义。
