title: Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea: the Connexin26/30 proteins are separately expressed in man.
abstract: Globally 360 million people have disabling hearing loss and, of these, 32 million are children. Human hearing relies on 15,000 hair cells that transduce mechanical vibrations to electrical signals in the auditory nerve. The process is powered by the endo-cochlear potential, which is produced by a vascularized epithelium that actively transports ions in conjunction with a gap junction (GJ) system. This "battery" is located "off-site" in the lateral wall of the cochlea. The GJ syncytium contains the GJ protein genes beta 2 (GJB2/connexin26 (Cx26)) and 6 (GJB6/connexin30 (Cx30)), which are commonly involved in hereditary deafness. Because the molecular arrangement of these proteins is obscure, we analyze GJ protein expression (Cx26/30) in human cochleae by using super-resolution structured illumination microscopy. At this resolution, the Cx26 and Cx30 proteins were visible as separate plaques, rather than being co-localized in heterotypic channels, as previously suggested. The Cx26 and Cx30 proteins thus seem not to be co-expressed but to form closely associated assemblies of GJ plaques. These results could assist in the development of strategies to treat genetic hearing loss in the future.
authors.affiliation: Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Department of Otolaryngology, Uppsala University Hospital, SE-751 85, Uppsala, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Department of Otolaryngology, Uppsala University Hospital, SE-751 85, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Edin
authors.affiliation: Science for Life laboratory, Department of Applied Physics, Royal Institute of Technology, Tomtebodavägen 23A, 17121, Solna, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Blom
authors.affiliation: Department of Immunology, Genetics and Pathology, Clinical Immunology, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors.forename: Peetra
authors.initials: P
authors.lastname: Magnusson
authors.affiliation: Department of Otolaryngology, Medical University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria.
authors.forename: Annelies
authors.initials: A
authors.lastname: Schrott-Fischer
authors.affiliation: Department of Otolaryngology, Medical University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria. rudolf.glueckert@i-med.ac.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Glueckert
authors.affiliation: Department of Otolaryngology, University of Minnesota, 121, Lions Research Bldg., 2001 Sixth St. SE, Minneapolis, MN 55455, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Santi
authors.affiliation: Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Department of Otolaryngology, Uppsala University Hospital, SE-751 85, Uppsala, Sweden.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Department of Otolaryngology, Uppsala University Hospital, SE-751 85, Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
authors.affiliation: Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Department of Otolaryngology, Uppsala University Hospital, SE-751 85, Uppsala, Sweden. helge.rask-andersen@akademiska.se.
authors.forename: Helge
authors.initials: H
authors.lastname: Rask-Andersen
mesh_terms: D000328:Adult; D000368:Aged; D003051:Cochlea / Q000378:metabolism* / Q000648:ultrastructure; D000072259:Connexin 26 / Q000378:metabolism*; D000075302:Connexin 30; D017630:Connexins / Q000378:metabolism*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017136:Ion Transport; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D008875:Middle Aged; D008954:Models, Biological; D015221:Potassium Channels / Q000378:metabolism
chemical_list: D000075302:Connexin 30; D017630:Connexins; C491020:GJB6 protein, human; D015221:Potassium Channels; D000072259:Connexin 26
keywords: Connexin (as elsewhere) 26/30; Human cochlea; Structured illumination microscopy