Date of Award
Doctor of Philosophy (PhD)
Cancer and Developmental Biology
Jian Zuo, Ph.D.
Kristin M. Hamre, Ph.D. Peter J. McKinnon, Ph.D. Beatriz Sosa-Pineda, Ph.D. Stanislav S. Zakharenko, Ph.D.
hair cells, mechanoeletrical transduction channel, polycystic kidney disease, polycystin-1, stereocilia
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 (TRP) family, PC-1 has also been hypothesized to play a role in the elusive mechanoelectrical transduction (MET) channel in inner ear hair cells based on PC-1 role of fluid flow sensing and calcium uptake into renal epithelial cells. However, two independent mouse lines with PC-1 mutations exhibit normal MET channel function despite hearing loss and ultra-structural abnormalities of stereocilia that remain properly polarized at adult ages. These findings indicate that PC-1 plays an essential role in stereocilia structure and maintenance, but not directly in MET channel function and planar cell polarity. We also demonstrate that PC-1 is co-localized with F-actin in hair cell stereocilia as well as with the actin based microvilli in a renal epithelia cell line. These results not only provide a unique hair cell stereocilia phenotype, but also ultimately may lead to a further understanding of the mechanisms behind polycystic kidney disease.
Steigelman, Katherine Ann , "The Role of Pkd1 in Mouse Inner Ear Hair Cells" (2010). Theses and Dissertations (ETD). Paper 253. http://dx.doi.org/10.21007/etd.cghs.2010.0298.