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Polarity Proteins Control Ciliogenesis via Kinesin Motor Interactions

2004; Elsevier BV; Volume: 14; Issue: 16 Linguagem: Inglês

10.1016/j.cub.2004.08.025

1879-0445

Shuling Fan, Toby W. Hurd, Chia‐Jen Liu, Samuel W. Straight, Thomas Weimbs, Elizabeth A. Hurd, Steven E. Domino, Ben Margolis,

Hippo pathway signaling and YAP/TAZ

Background: Cilia are specialized organelles that play a fundamental role in several mammalian processes including left-right axis determination, sperm motility, and photoreceptor maintenance. Mutations in cilia-localized proteins have been linked to human diseases including cystic kidney disease and retinitis pigmentosa. Retinitis pigmentosa can be caused by loss-of-function mutations in the polarity protein Crumbs1 (CRB1), but the exact role of CRB1 in retinal function is unclear.Results: Here we show that CRB3, a CRB1-related protein found in epithelia, is localized to cilia and required for proper cilia formation. We also find that the Crumbs-associated Par3/Par6/aPKC polarity cassette localizes to cilia and regulates ciliogenesis. In addition, there appears to be an important role for the polarity-regulating 14-3-3 proteins in this process. Finally, we can demonstrate association of these polarity proteins with microtubules and the microtubular motor KIF3/Kinesin-II.Conclusions: Our findings point to a heretofore unappreciated role for polarity proteins in cilia formation and provide a potentially unique insight into the pathogenesis of human kidney and retinal disease.