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- Title
Polycystin-1 Is Required for Stereocilia Structure But Not for Mechanotransduction in Inner Ear Hair Cells.
- Authors
Steigelman, Katherine A.; Lelli, Andrea; Xudong Wu; Jiangang Gao; Lin, Susan; Piontek, Klaus; Wodarczyk, Claas; Boletta, Alessandra; Hyunho Kim; Feng Qian; Germino, Gregory; Géléoc, Gwenaélle S. G.; Holt, Jeffrey R.; Jian Zuo
- 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.
- Subjects
GENETIC transduction; INNER ear; HAIR cells; POLYCYSTIC kidney disease; LABORATORY mice
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 34, p12251
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.6531-10.2011