title: Generation of somatic electromechanical force by outer hair cells may be influenced by prestin-CASK interaction at the basal junction with the Deiter's cell.
abstract: The motor protein, prestin, situated in the basolateral plasma membrane of cochlear outer hair cells (OHCs), underlies the generation of somatic, voltage-driven mechanical force, the basis for the exquisite sensitivity, frequency selectivity and dynamic range of mammalian hearing. The molecular and structural basis of the ontogenetic development of this electromechanical force has remained elusive. The present study demonstrates that this force is significantly reduced when the immature subcellular distribution of prestin found along the entire plasma membrane persists into maturity, as has been described in previous studies under hypothyroidism. This observation suggests that cochlear amplification is critically dependent on the surface expression and distribution of prestin. Searching for proteins involved in organizing the subcellular localization of prestin to the basolateral plasma membrane, we identified cochlear expression of a novel truncated prestin splice isoform named prestin 9b (Slc26A5d) that contains a putative PDZ domain-binding motif. Using prestin 9b as the bait in a yeast two-hybrid assay, we identified a calcium/calmodulin-dependent serine protein kinase (CASK) as an interaction partner of prestin. Co-immunoprecipitation assays showed that CASK and prestin 9b can interact with full-length prestin. CASK was co-localized with prestin in a membrane domain where prestin-expressing OHC membrane abuts prestin-free OHC membrane, but was absent from this area for thyroid hormone deficiency. These findings suggest that CASK and the truncated prestin splice isoform contribute to confinement of prestin to the basolateral region of the plasma membrane. By means of such an interaction, the basal junction region between the OHC and its Deiter's cell may contribute to efficient generation of somatic electromechanical force.
authors.affiliation: Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.
authors.forename: Jelka
authors.initials: J
authors.lastname: Cimerman
authors.forename: Jörg
authors.initials: J
authors.lastname: Waldhaus
authors.forename: Csaba
authors.initials: C
authors.lastname: Harasztosi
authors.forename: Susanne V
authors.initials: SV
authors.lastname: Duncker
authors.forename: Juliane
authors.initials: J
authors.lastname: Dettling
authors.forename: Paulina
authors.initials: P
authors.lastname: Heidrych
authors.forename: Andreas
authors.initials: A
authors.lastname: Bress
authors.forename: Claudia
authors.initials: C
authors.lastname: Gampe-Braig
authors.forename: Gerhard
authors.initials: G
authors.lastname: Frank
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Gummer
authors.forename: Dominik
authors.initials: D
authors.lastname: Oliver
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zimmermann
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004560:Electricity; D005260:Female; D051528:Guanylate Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018072:Hair Cells, Auditory, Outer / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D055595:Mechanical Phenomena; D051379:Mice; D008815:Mice, Inbred Strains; D020409:Molecular Motor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000076988:Sulfate Transporters; D003689:Vestibular Nucleus, Lateral / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; C498719:SLC26A5 protein, human; C409207:Slc26a5 protein, rat; D000076988:Sulfate Transporters; C106868:CASK kinases; D051528:Guanylate Kinases
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