Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.
The most impressive property of outer hair cells (OHCs) is their ability to change their length at high acoustic frequencies, thus providing the exquisite sensitivity and frequency-resolving capacity of the mammalian hearing organ. Prestin, a protein related to a sulfate/anion transport protein, recently has been identified and proposed as the OHC motor molecule. Homology searches of 1.5 kb of genomic DNA 5' of the coding region of the prestin gene allowed the identification of a thyroid hormone (TH) response element (TRE) in the first intron upstream of the prestin ATG codon. Prestin(TRE) bound TH receptors as a monomer or presumptive heterodimer and mediated a triiodothyronine-dependent transactivation of a heterologous promotor in response to triiodothyronine receptors alpha and beta. Retinoid X receptor-alpha had an additive effect. Expression of prestin mRNA and prestin protein was reduced strongly in the absence of TH. Although prestin protein typically was redistributed to the lateral membrane before the onset of hearing, an immature pattern of prestin protein distribution across the entire OHC membrane was noted in hypothyroid rats. The data suggest TH as a first transcriptional regulator of the motor protein prestin and as a direct or indirect modulator of subcellular prestin distribution.
Weber
Thomas
T
Department of Otolaryngology, Laboratory of Molecular Neurobiology, University of Tübingen, Röntgenweg 11, 72076 Tübingen, Germany.
Zimmermann
Ulrike
U
Winter
Harald
H
Mack
Andreas
A
Köpschall
Iris
I
Rohbock
Karin
K
Zenner
Hans-Peter
HP
Knipper
Marlies
M
D024506:5' Flanking Region; D000818:Animals; D027321:Anion Transport Proteins; D001483:Base Sequence; D002460:Cell Line; D003051:Cochlea / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D000076988:Sulfate Transporters; D015534:Trans-Activators / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D027321:Anion Transport Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; C498719:SLC26A5 protein, human; C409207:Slc26a5 protein, rat; D000076988:Sulfate Transporters; D015534:Trans-Activators; D014284:Triiodothyronine; D008156:Luciferases