Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells

Katherine A. Steigelman, Andrea Lelli, Xudong Wu, Jiangang Gao, Susan Lin, Klaus Piontek, Claas Wodarczyk, Alessandra Boletta, Hyunho Kim, Feng Qian, Gregory Germino, Gwenälle S G Géléoc, Jeffrey R. Holt, Jian Zuo

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)12241-12250
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number34
DOIs
StatePublished - Aug 24 2011

Fingerprint

Inner Auditory Hair Cells
Stereocilia
Polycystic Kidney Diseases
Inner Ear
Kidney
Cell Polarity
Cochlea
Hemagglutinins
Microvilli
Hearing Loss
Actins
Epithelial Cells
Maintenance
Genes
Proteins
polycystic kidney disease 1 protein

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells. / Steigelman, Katherine A.; Lelli, Andrea; Wu, Xudong; Gao, Jiangang; Lin, Susan; Piontek, Klaus; Wodarczyk, Claas; Boletta, Alessandra; Kim, Hyunho; Qian, Feng; Germino, Gregory; Géléoc, Gwenälle S G; Holt, Jeffrey R.; Zuo, Jian.

In: Journal of Neuroscience, Vol. 31, No. 34, 24.08.2011, p. 12241-12250.

Research output: Contribution to journalArticle

Steigelman, KA, Lelli, A, Wu, X, Gao, J, Lin, S, Piontek, K, Wodarczyk, C, Boletta, A, Kim, H, Qian, F, Germino, G, Géléoc, GSG, Holt, JR & Zuo, J 2011, 'Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells', Journal of Neuroscience, vol. 31, no. 34, pp. 12241-12250. https://doi.org/10.1523/JNEUROSCI.6531-10.2011
Steigelman, Katherine A. ; Lelli, Andrea ; Wu, Xudong ; Gao, Jiangang ; Lin, Susan ; Piontek, Klaus ; Wodarczyk, Claas ; Boletta, Alessandra ; Kim, Hyunho ; Qian, Feng ; Germino, Gregory ; Géléoc, Gwenälle S G ; Holt, Jeffrey R. ; Zuo, Jian. / Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 34. pp. 12241-12250.
@article{ba25853f038546b89517aa6ee360637a,
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.",
author = "Steigelman, {Katherine A.} and Andrea Lelli and Xudong Wu and Jiangang Gao and Susan Lin and Klaus Piontek and Claas Wodarczyk and Alessandra Boletta and Hyunho Kim and Feng Qian and Gregory Germino and G{\'e}l{\'e}oc, {Gwen{\"a}lle S G} and Holt, {Jeffrey R.} and Jian Zuo",
year = "2011",
month = "8",
day = "24",
doi = "10.1523/JNEUROSCI.6531-10.2011",
language = "English (US)",
volume = "31",
pages = "12241--12250",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "34",

}

TY - JOUR

T1 - Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells

AU - Steigelman, Katherine A.

AU - Lelli, Andrea

AU - Wu, Xudong

AU - Gao, Jiangang

AU - Lin, Susan

AU - Piontek, Klaus

AU - Wodarczyk, Claas

AU - Boletta, Alessandra

AU - Kim, Hyunho

AU - Qian, Feng

AU - Germino, Gregory

AU - Géléoc, Gwenälle S G

AU - Holt, Jeffrey R.

AU - Zuo, Jian

PY - 2011/8/24

Y1 - 2011/8/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052153568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052153568&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.6531-10.2011

DO - 10.1523/JNEUROSCI.6531-10.2011

M3 - Article

VL - 31

SP - 12241

EP - 12250

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 34

ER -