title: Promyelocytic leukemia zinc finger protein localizes to the cochlear outer hair cells and interacts with prestin, the outer hair cell motor protein.
abstract: 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.
authors.affiliation: Inner Ear Research Laboratory, ENT Department, University Hospital Zurich, NORD2 Frauenklinikstr. 24, 8091 Zurich, Switzerland. Ivana.Nagy@usz.ch
authors.forename: Ivana
authors.initials: I
authors.lastname: Nagy
authors.forename: Morana
authors.initials: M
authors.lastname: Bodmer
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmid
authors.forename: Daniel
authors.initials: D
authors.lastname: Bodmer
mesh_terms: 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
chemical_list: D027321:Anion Transport Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters; D014157:Transcription Factors