0536141 - ÚMG 2021 RIV US eng J - Journal Article
Prasai, Avishek - Schmidt Černohorská, Markéta - Ruppová, Klára - Niederlová, Veronika - Andělová, Monika - Dráber, Peter - Štěpánek, Ondřej - Huranová, Martina
The BBSome assembly is spatially controlled by BBS1 and BBS4 in human cells.
Journal of Biological Chemistry. Roč. 295, č. 42 (2020), s. 14279-14290. ISSN 0021-9258. E-ISSN 1083-351X
R&D Projects: GA ČR(CZ) GJ17-20613Y
Institutional support: RVO:68378050
Keywords : Bardet-Biedl Syndrome * BBSome * assembly * cilium * ciliopathy * protein sorting * protein assembly * primary cilium * microscopic imaging * genetic disease * Bardet-Biedl syndrome
OECD category: Cell biology
Impact factor: 5.157, year: 2020 ; AIS: 1.578, rok: 2020
Method of publishing: Limited access
Result website:
https://www.jbc.org/content/295/42/14279DOI: https://doi.org/10.1074/jbc.RA120.013905

Bardet-Biedl syndrome (BBS) is a pleiotropic ciliopathy caused by dysfunction of primary cilia. More than half of BBS patients carry mutations in one of eight genes encoding for subunits of a protein complex, the BBSome, which mediates trafficking of ciliary cargoes. In this study, we elucidated the mechanisms of the BBSome assembly in living cells and how this process is spatially regulated. We generated a large library of human cell lines deficient in a particular BBSome subunit and expressing another subunit tagged with a fluorescent protein. We analyzed these cell lines utilizing biochemical assays, conventional and expansion microscopy, and quantitative fluorescence microscopy techniques: fluorescence recovery after photobleaching and fluorescence correlation spectroscopy. Our data revealed that the BBSome formation is a sequential process. We show that the pre-BBSome is nucleated by BBS4 and assembled at pericentriolar satellites, followed by the translocation of the BBSome into the ciliary base mediated by BBS1. Our results provide a framework for elucidating how BBS-causative mutations interfere with the biogenesis of the BBSome.
Permanent Link: http://hdl.handle.net/11104/0313965