Nature Genetics
36, 462 - 470 (2004)
Published online: 25 April 2004; | doi:10.1038/ng1352
The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progressionJun Chul Kim1, 6, Jose L Badano2, 6, Sonja Sibold3, 6, Muneer A Esmail1, Josephine Hill3, Bethan E Hoskins3, Carmen C Leitch2, Kerrie Venner4, Stephen J Ansley2, Alison J Ross3, Michel R Leroux1, Nicholas Katsanis2, 5
& Philip L Beales31
Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Dr., Burnaby
BC, V5A 1S6, Canada. 2
Institute of Genetic Medicine, Johns Hopkins University, 600 North Wolfe Street, Baltimore, Maryland
21287, USA. 3
Molecular Medicine Unit, Institute of Child Health, University College London, London
WC1N 1EH, UK. 4
Department of Electron Microscopy, Institute of Neurology, Queens Square, London, UK. 5
Wilmer Eye Institute, Johns Hopkins University, 600 North Wolfe Street, Baltimore, Maryland
21287, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Michel R Leroux leroux@sfu.ca or Nicholas Katsanis katsanis@jhmi.eduBBS4 is one of several proteins that cause Bardet-Biedl syndrome (BBS), a multisystemic disorder of genetic and clinical complexity. Here we show that BBS4 localizes to the centriolar satellites of centrosomes and basal bodies of primary cilia, where it functions as an adaptor of the p150glued subunit of the dynein transport machinery to recruit PCM1 (pericentriolar material 1 protein) and its associated cargo to the satellites. Silencing of BBS4 induces PCM1 mislocalization and concomitant deanchoring of centrosomal microtubules, arrest in cell division and apoptotic cell death. Expression of two truncated forms of BBS4 that are similar to those found in some individuals with BBS had a similar effect on PCM1 and microtubules. Our findings indicate that defective targeting or anchoring of pericentriolar proteins and microtubule disorganization contribute to the BBS phenotype and provide new insights into possible causes of familial obesity, diabetes and retinal degeneration.
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