Polarity proteins control ciliogenesis via kinesin motor interactions

Curr Biol. 2004 Aug 24;14(16):1451-61. doi: 10.1016/j.cub.2004.08.025.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Animals
  • Blotting, Western
  • Calcium-Binding Proteins / metabolism
  • Cell Polarity / genetics*
  • Cells, Cultured
  • Cilia / metabolism*
  • Cilia / physiology*
  • Dogs
  • Electrophoresis, Polyacrylamide Gel
  • Immunohistochemistry
  • Kidney / metabolism
  • Kinesin
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Microtubules / metabolism
  • Muscle Proteins / metabolism
  • Mutation / genetics
  • Oligonucleotides
  • Precipitin Tests
  • Protein Kinase C / metabolism*
  • Spermatozoa / physiology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • 14-3-3 Proteins
  • CRB3 protein, human
  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Muscle Proteins
  • Oligonucleotides
  • kinesin-II
  • Tyrosine 3-Monooxygenase
  • PKC-3 protein
  • Protein Kinase C
  • Kinesin