The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression.

Published

Journal Article

BBS4 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 p150(glued) 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.

Full Text

Duke Authors

Cited Authors

  • Kim, JC; Badano, JL; Sibold, S; Esmail, MA; Hill, J; Hoskins, BE; Leitch, CC; Venner, K; Ansley, SJ; Ross, AJ; Leroux, MR; Katsanis, N; Beales, PL

Published Date

  • May 2004

Published In

Volume / Issue

  • 36 / 5

Start / End Page

  • 462 - 470

PubMed ID

  • 15107855

Pubmed Central ID

  • 15107855

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng1352

Language

  • eng