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The actin-bundling protein Fascin-1 modulates ciliary signalling

Journal of Molecular Cell Biology 2023年第4期15卷 1-16页

作者： Lena Brücker Stefanie Kornelia Becker vanessa maissl Gregory Harms Maddy Parsons Helen Louise May-Simera Cilia Cell Biology Institute of Molecular PhysiologyJohannes Gutenberg University Mainz55128 MainzGermany Imaging Core Facility Cell Biology UnitUniversity Medical CentreJohannes Gutenberg University Mainz55101 MainzGermany Randall Centre for Cell and Molecular Biophysics King's College LondonLondon SE11ULUK

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.

关键词： cilia actin Wnt signalling ciliopathy Bardet–Biedl syndrome filopodia

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