Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells

Herald Winter, Claudia Braig, Ulrike Zimmermann, Hyun Soon Geisler, Jürgen Theodor Fränzer, Thomas Weber, Matthias Ley, Jutta Engel, Martina Knirsch, Karl Bauer, Stephanie Christ, Edward J. Walsh, JoAnn McGee, Iris Köpschall, Karin Rohbock, Marlies Knipper

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Thyroid hormone (TH or T3) and TH-receptor β (TRβ) have been reported to be relevant for cochlear development and hearing function. Mutations in the TRβ gene result in deafness associated with resistance to TH syndrome. The effect of TRα1 on neither hearing function nor cochlear T3 target genes has been described to date. It is also uncertain whether TRα1 and TRβ can act simultaneously on different target genes within a single cell. We focused on two concomitantly expressed outer hair cell genes, the potassium channel Kcnq4 and the motor protein prestin Slc26a5. In outer hair cells, TH enhanced the expression of the prestin gene through TRβ. Simultaneously Kcnq4 expression was activated in the same cells by derepression of TRα1 aporeceptors mediated by an identified TH-response element, which modulates KCNQ4 promoter activity. We show that T3 target genes can differ in their sensitivity to TH receptors having the ligand either bound (holoreceptors) or not bound (aporeceptors) within single cells, and suggest a role for TRα1 in final cell differentiation.

Original languageEnglish (US)
Pages (from-to)2975-2984
Number of pages10
JournalJournal of cell science
Volume119
Issue number14
DOIs
StatePublished - Jul 15 2006

Fingerprint

Outer Auditory Hair Cells
Thyroid Hormone Receptors
Gene Expression
Genes
Cochlea
Hearing
Potassium Channels
Response Elements
Deafness
Thyroid Hormones
Cell Differentiation
Ligands
Mutation

Keywords

  • Final differentiation
  • KCNQ4
  • Prestin
  • TR aporeceptors

ASJC Scopus subject areas

  • Cell Biology

Cite this

Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells. / Winter, Herald; Braig, Claudia; Zimmermann, Ulrike; Geisler, Hyun Soon; Fränzer, Jürgen Theodor; Weber, Thomas; Ley, Matthias; Engel, Jutta; Knirsch, Martina; Bauer, Karl; Christ, Stephanie; Walsh, Edward J.; McGee, JoAnn; Köpschall, Iris; Rohbock, Karin; Knipper, Marlies.

In: Journal of cell science, Vol. 119, No. 14, 15.07.2006, p. 2975-2984.

Research output: Contribution to journalArticle

Winter, H, Braig, C, Zimmermann, U, Geisler, HS, Fränzer, JT, Weber, T, Ley, M, Engel, J, Knirsch, M, Bauer, K, Christ, S, Walsh, EJ, McGee, J, Köpschall, I, Rohbock, K & Knipper, M 2006, 'Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells', Journal of cell science, vol. 119, no. 14, pp. 2975-2984. https://doi.org/10.1242/jcs.03013
Winter, Herald ; Braig, Claudia ; Zimmermann, Ulrike ; Geisler, Hyun Soon ; Fränzer, Jürgen Theodor ; Weber, Thomas ; Ley, Matthias ; Engel, Jutta ; Knirsch, Martina ; Bauer, Karl ; Christ, Stephanie ; Walsh, Edward J. ; McGee, JoAnn ; Köpschall, Iris ; Rohbock, Karin ; Knipper, Marlies. / Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells. In: Journal of cell science. 2006 ; Vol. 119, No. 14. pp. 2975-2984.
@article{252cce19505d411abd0f3368d8201fc3,
title = "Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells",
abstract = "Thyroid hormone (TH or T3) and TH-receptor β (TRβ) have been reported to be relevant for cochlear development and hearing function. Mutations in the TRβ gene result in deafness associated with resistance to TH syndrome. The effect of TRα1 on neither hearing function nor cochlear T3 target genes has been described to date. It is also uncertain whether TRα1 and TRβ can act simultaneously on different target genes within a single cell. We focused on two concomitantly expressed outer hair cell genes, the potassium channel Kcnq4 and the motor protein prestin Slc26a5. In outer hair cells, TH enhanced the expression of the prestin gene through TRβ. Simultaneously Kcnq4 expression was activated in the same cells by derepression of TRα1 aporeceptors mediated by an identified TH-response element, which modulates KCNQ4 promoter activity. We show that T3 target genes can differ in their sensitivity to TH receptors having the ligand either bound (holoreceptors) or not bound (aporeceptors) within single cells, and suggest a role for TRα1 in final cell differentiation.",
keywords = "Final differentiation, KCNQ4, Prestin, TR aporeceptors",
author = "Herald Winter and Claudia Braig and Ulrike Zimmermann and Geisler, {Hyun Soon} and Fr{\"a}nzer, {J{\"u}rgen Theodor} and Thomas Weber and Matthias Ley and Jutta Engel and Martina Knirsch and Karl Bauer and Stephanie Christ and Walsh, {Edward J.} and JoAnn McGee and Iris K{\"o}pschall and Karin Rohbock and Marlies Knipper",
year = "2006",
month = "7",
day = "15",
doi = "10.1242/jcs.03013",
language = "English (US)",
volume = "119",
pages = "2975--2984",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "14",

}

TY - JOUR

T1 - Thyroid hormone receptors TRα1 and TRβ differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells

AU - Winter, Herald

AU - Braig, Claudia

AU - Zimmermann, Ulrike

AU - Geisler, Hyun Soon

AU - Fränzer, Jürgen Theodor

AU - Weber, Thomas

AU - Ley, Matthias

AU - Engel, Jutta

AU - Knirsch, Martina

AU - Bauer, Karl

AU - Christ, Stephanie

AU - Walsh, Edward J.

AU - McGee, JoAnn

AU - Köpschall, Iris

AU - Rohbock, Karin

AU - Knipper, Marlies

PY - 2006/7/15

Y1 - 2006/7/15

N2 - Thyroid hormone (TH or T3) and TH-receptor β (TRβ) have been reported to be relevant for cochlear development and hearing function. Mutations in the TRβ gene result in deafness associated with resistance to TH syndrome. The effect of TRα1 on neither hearing function nor cochlear T3 target genes has been described to date. It is also uncertain whether TRα1 and TRβ can act simultaneously on different target genes within a single cell. We focused on two concomitantly expressed outer hair cell genes, the potassium channel Kcnq4 and the motor protein prestin Slc26a5. In outer hair cells, TH enhanced the expression of the prestin gene through TRβ. Simultaneously Kcnq4 expression was activated in the same cells by derepression of TRα1 aporeceptors mediated by an identified TH-response element, which modulates KCNQ4 promoter activity. We show that T3 target genes can differ in their sensitivity to TH receptors having the ligand either bound (holoreceptors) or not bound (aporeceptors) within single cells, and suggest a role for TRα1 in final cell differentiation.

AB - Thyroid hormone (TH or T3) and TH-receptor β (TRβ) have been reported to be relevant for cochlear development and hearing function. Mutations in the TRβ gene result in deafness associated with resistance to TH syndrome. The effect of TRα1 on neither hearing function nor cochlear T3 target genes has been described to date. It is also uncertain whether TRα1 and TRβ can act simultaneously on different target genes within a single cell. We focused on two concomitantly expressed outer hair cell genes, the potassium channel Kcnq4 and the motor protein prestin Slc26a5. In outer hair cells, TH enhanced the expression of the prestin gene through TRβ. Simultaneously Kcnq4 expression was activated in the same cells by derepression of TRα1 aporeceptors mediated by an identified TH-response element, which modulates KCNQ4 promoter activity. We show that T3 target genes can differ in their sensitivity to TH receptors having the ligand either bound (holoreceptors) or not bound (aporeceptors) within single cells, and suggest a role for TRα1 in final cell differentiation.

KW - Final differentiation

KW - KCNQ4

KW - Prestin

KW - TR aporeceptors

UR - http://www.scopus.com/inward/record.url?scp=33746835277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746835277&partnerID=8YFLogxK

U2 - 10.1242/jcs.03013

DO - 10.1242/jcs.03013

M3 - Article

C2 - 16803873

AN - SCOPUS:33746835277

VL - 119

SP - 2975

EP - 2984

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 14

ER -