Polycystin-1 Is Required for Stereocilia Structure But Not for Mechanotransduction in Inner Ear Hair Cells
- Katherine A. Steigelman1,2,
- Andrea Lelli3,
- Xudong Wu1,
- Jiangang Gao1,
- Susan Lin1,
- Klaus Piontek4,
- Claas Wodarczyk5,
- Alessandra Boletta5,
- Hyunho Kim4,
- Feng Qian4,
- Gregory Germino4,6,
- Gwenaëlle S. G. Géléoc3,
- Jeffrey R. Holt3, and
- Jian Zuo1
- 1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,
- 2Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163,
- 3Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908,
- 4Division of Nephrology, Johns Hopkins University, Baltimore, Maryland 21205,
- 5Dulbecco Telethon Institute, Dibit San Raffaele Scientific Institute, 20132 Milan, Italy, and
- 6National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892
-
Author contributions: K.A.S., X.W., F.Q., J.R.H., and J.Z. designed research; K.A.S., A.L., S.L., X.W., J.G., and G.S.G.G. performed research; K.A.S., J.G., K.P., C.W., A.B., H.K., F.Q., and G.G. contributed unpublished reagents/analytic tools; K.A.S. and A.L. analyzed data; K.A.S. and J.Z. wrote the paper.
Abstract
The polycystic kidney disease-1 (Pkd1) gene encodes a large transmembrane protein (polycystin-1, or PC-1) that is reported to function as a fluid flow sensor in the kidney. As a member of the transient receptor potential family, PC-1 has also been hypothesized to play a role in the elusive mechanoelectrical transduction (MET) channel in inner ear hair cells. Here, we analyze two independent mouse models of PC-1, a knock-in (KI) mutant line and a hair cell-specific inducible Cre-mediated knock-out line. Both models exhibit normal MET channel function at neonatal ages despite hearing loss and ultrastructural abnormalities of sterecilia that remain properly polarized at adult ages. These findings demonstrate that PC-1 plays an essential role in stereocilia structure and maintenance but not directly in MET channel function or planar cell polarity. We also demonstrate that PC-1 is colocalized with F-actin in hair cell stereocilia in vivo, using a hemagglutinin-tagged PC-1 KI mouse model, and in renal epithelial cell microvilli in vitro. These results not only demonstrate a novel role for PC-1 in the cochlea, but also suggest insight into the development of polycystic kidney disease.
- Received December 13, 2010.
- Revision received June 26, 2011.
- Accepted June 29, 2011.
- Copyright © 2011 the authors 0270-6474/11/3112241-10$15.00/0
