Promyelocytic leukemia zinc finger protein localizes to the cochlear outer hair cells and interacts with prestin, the outer hair cell motor protein.
Hair cells in the auditory sensory organ are specialized mechanoreceptors common to mammalian and non-mammalian species. The mammalian cochlear outer hair cells (OHC) possess a distinct motile property, dubbed membrane-based electromotility, that enhances the receptor function. This electromotility is believed to be the basis of cochlear amplification that increases sensitivity of the mammalian ear to sound. Prestin, a unique voltage-sensitive motor molecule localized in the lateral membrane of OHC, is presumably responsible for OHC electromotility. It has been documented that prestin null-animals lack electromotility and suffer from approximately 50 dB loss of hearing sensitivity. To identify proteins that interact with prestin we carried out a yeast two-hybrid library screen using the C-terminal intracellular domain of prestin as bait. Seven bait-dependent prey clones were identified independently. Further analysis revealed that they encode partially over-lapping regions of a single protein: a transcriptional repressor, promyleocytic leukemia zinc finger protein (PLZF). PLZF encodes a POZ/domain Kruppel-type zinc finger transcription factor reported to have pro-apoptotic and anti-proliferative activity. The interaction between endogenous prestin and PLZF proteins in the cochlea was confirmed by co-immunoprecipitation using organ of Corti lysates. Furthermore, immunohistochemical studies strongly suggest that PLZF co-localizes with prestin near the lateral membrane of cochlear OHC. The physiological significance of this interaction remains to be explored.
Nagy
Ivana
I
Inner Ear Research Laboratory, ENT Department, University Hospital Zurich, NORD2 Frauenklinikstr. 24, 8091 Zurich, Switzerland. Ivana.Nagy@usz.ch
Bodmer
Morana
M
Schmid
Stephan
S
Bodmer
Daniel
D
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D027321:Anion Transport Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters; D014157:Transcription Factors