title: Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells.
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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Steigelman
authors.forename: Andrea
authors.initials: A
authors.lastname: Lelli
authors.forename: Xudong
authors.initials: X
authors.lastname: Wu
authors.forename: Jiangang
authors.initials: J
authors.lastname: Gao
authors.forename: Susan
authors.initials: S
authors.lastname: Lin
authors.forename: Klaus
authors.initials: K
authors.lastname: Piontek
authors.forename: Claas
authors.initials: C
authors.lastname: Wodarczyk
authors.forename: Alessandra
authors.initials: A
authors.lastname: Boletta
authors.forename: Hyunho
authors.initials: H
authors.lastname: Kim
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Gregory
authors.initials: G
authors.lastname: Germino
authors.forename: Gwenaëlle S G
authors.initials: GS
authors.lastname: Géléoc
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Holt
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009925:Organ of Corti / Q000502:physiology*; D050396:TRPP Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D050396:TRPP Cation Channels