UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Bardet-Biedl syndrome proteins control cilia length through regulation of actin polymerisation.

Hernandez-Hernandez, V; Pravincumar, P; Diaz-Font, A; May-Simera, H; Jenkins, D; Knight, M; Beales, PL; (2013) Bardet-Biedl syndrome proteins control cilia length through regulation of actin polymerisation. Human Molecular Genetics , 22 (19) pp. 3858-3868. 10.1093/hmg/ddt241. Green open access

[thumbnail of Hum._Mol._Genet.-2013-Hernandez-Hernandez-3858-68.pdf]
Preview
PDF
Hum._Mol._Genet.-2013-Hernandez-Hernandez-3858-68.pdf

Download (1MB)
[thumbnail of Supplementary Movie 10] AVI video (Supplementary Movie 10)
ddt241supp_video10.avi

Download (395kB)
[thumbnail of Supplementary Movie 9] AVI video (Supplementary Movie 9)
ddt241supp_video9.avi

Download (1MB)
[thumbnail of Supplementary Movie 8] AVI video (Supplementary Movie 8)
ddt241supp_video8.avi

Download (409kB)
[thumbnail of Supplementary Movie 7] AVI video (Supplementary Movie 7)
ddt241supp_video7.avi

Download (1MB)
[thumbnail of Supplementary Movie 6] MP4 video (Supplementary Movie 6)
ddt241supp_video6.mp4

Download (619kB)
[thumbnail of Supplementary Movie 5] AVI video (Supplementary Movie 5)
ddt241supp_video5.avi

Download (2MB)
[thumbnail of Supplementary Movie 4] AVI video (Supplementary Movie 4)
ddt241supp_video4.avi

Download (2MB)
[thumbnail of Supplementary Movie 3] MP4 video (Supplementary Movie 3)
ddt241supp_video3.mp4

Download (924kB)
[thumbnail of Supplementary Movie 2] MP4 video (Supplementary Movie 2)
ddt241supp_video2.mp4

Download (715kB)
[thumbnail of Supplementary Movie 1] MP4 video (Supplementary Movie 1)
ddt241supp_video1.mp4

Download (2MB)
[thumbnail of Supplementary Data ] Other (Supplementary Data )
ddt241supp.docx

Download (7MB)

Abstract

Primary cilia are cellular appendages important for signal transduction and sensing the environment. Bardet-Biedl syndrome proteins form a complex that is important for several cytoskeleton-related processes such as ciliogenesis, cell migration and division. However, the mechanisms by which BBS proteins may regulate the cytoskeleton remain unclear. We discovered that Bbs4 and Bbs6 deficient renal medullary cells display a characteristic behaviour comprising poor migration, adhesion and division with an inability to form lamellipodial and filopodial extensions. Moreover, fewer mutant cells were ciliated (48% ± 6 for wild-type cells vs 23% ± 7 for Bbs4 null cells; P-value < 0.0001) and their cilia were shorter (2.55&emsp14;μm ± 0.41 for wild-type cells vs 2.16&emsp14;μm ± 0.23 for Bbs4 null cells; P-value < 0.0001). Whilst the microtubular cytoskeleton and cortical actin were intact, actin stress fibre formation was severely disrupted, forming abnormal apical stress fibre aggregates. Furthermore, we observed over-abundant focal adhesions in Bbs4, Bbs6 and Bbs8-deficient cells. In view of these findings and the role of RhoA in regulation of actin filament polymerisation, we showed that RhoA-GTP levels were highly upregulated in the absence of Bbs proteins. Upon treatment of Bbs4-deficient cells with chemical inhibitors of RhoA, we were able to restore cilia length and number as well as the integrity of the actin cytoskeleton. Together these findings indicate that Bbs proteins play a central role in the regulation of the actin cytoskeleton and control cilia length through alteration of RhoA levels.

Type: Article
Title: Bardet-Biedl syndrome proteins control cilia length through regulation of actin polymerisation.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/hmg/ddt241
Publisher version: http://dx.doi.org/10.1093/hmg/ddt241
Language: English
Additional information: © The Author 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1395342
Downloads since deposit
353Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item