Polarity proteins control ciliogenesis via kinesin motor interactions.
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.
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Shuling
S
Fan
Toby W
TW
Hurd
Chia-Jen
CJ
Liu
Samuel W
SW
Straight
Thomas
T
Weimbs
Elizabeth A
EA
Hurd
Steven E
SE
Domino
Ben
B
Margolis
D048948:14-3-3 Proteins; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics*; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism* / Q000502:physiology*; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D016547:Kinesins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009841:Oligonucleotides; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D013094:Spermatozoa / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D048948:14-3-3 Proteins; C472002:CRB3 protein, human; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009124:Muscle Proteins; D009841:Oligonucleotides; C074152:kinesin-II; D014446:Tyrosine 3-Monooxygenase; C115015:PKC-3 protein; D011493:Protein Kinase C; D016547:Kinesins