TY - JOUR
T1 - The actin-bundling protein Fascin-1 modulates ciliary signalling
AU - Brücker, Lena
AU - Becker, Stefanie Kornelia
AU - Maissl, Vanessa
AU - Harms, Gregory
AU - Parsons, Madeline
AU - May-Simera, Helen Louise
N1 - Funding Information:
This work was supported by grants from Johannes Gutenberg University Mainz, Alexander von Humboldt Foundation (Sofja Kovalevskaja Award), Hanns Seidel Foundation, and Sibylle Kalkhof-Rose Foundation. This project was further funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, GRK2526/1-Projectnr. 407023052).
Publisher Copyright:
© 2023 The Author(s) (2023).
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85170294610&partnerID=8YFLogxK
U2 - 10.1093/jmcb/mjad022
DO - 10.1093/jmcb/mjad022
M3 - Article
SN - 1674-2788
VL - 15
JO - Journal of Molecular Cell Biology
JF - Journal of Molecular Cell Biology
IS - 4
M1 - mjad022
ER -