Molecular composition and distribution of gap junctions in the sensory epithelium of the human cochlea-a super-resolution structured illumination microscopy (SR-SIM) study

Upsala Journal of Medical Sciences
Wei LiuHelge Rask-Andersen

Abstract

Mutations in the GJB2 gene, which encodes the Connexin26 (Cx26) protein, are the most common cause of childhood hearing loss in American and European populations. The cochlea contains a gap junction (GJ) network in the sensory epithelium and two connective tissue networks in the lateral wall and spiral limbus. The syncytia contain the GJ proteins beta 2 (GJB2/Cx26) and beta 6 (GJB6/Cx30). Our knowledge of their expression in humans is insufficient due to the limited availability of tissue. Here, we sought to establish the molecular arrangement of GJs in the epithelial network of the human cochlea using surgically obtained samples. We analyzed Cx26 and Cx30 expression in GJ networks in well-preserved adult human auditory sensory epithelium using confocal, electron, and super-resolution structured illumination microscopy (SR-SIM). Cx30 plaques (<5 μm) dominated, while Cx26 plaques were subtle and appeared as 'mini-junctions' (2-300 nm). 3-D volume rendering of Z-stacks and orthogonal projections from single optical sections suggested that the GJs are homomeric/homotypic and consist of assemblies of identical GJs composed of either Cx26 or Cx30. Occasionally, the two protein types were co-expressed, suggesting functional cooperati...Continue Reading

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Citations

Mar 15, 2018·Upsala Journal of Medical Sciences·Sumit AgrawalHao Li
Jan 10, 2018·Frontiers in Molecular Neuroscience·Francisco J Del Castillo, Ignacio Del Castillo
Feb 21, 2018·Cell and Tissue Research·Wei LiuHelge Rask-Andersen
Sep 6, 2018·Cold Spring Harbor Perspectives in Medicine·Fabio Mammano
Feb 19, 2019·Frontiers in Immunology·Charlotta Kämpfe NordströmHelge Rask-Andersen
Jul 30, 2019·Frontiers in Neurology·Wei LiuHelge Rask-Andersen
Feb 9, 2018·Tissue Barriers·Emily I BartleAlexa L Mattheyses
Aug 30, 2017·Frontiers in Molecular Neuroscience·Wei LiuHelge Rask-Andersen
Aug 24, 2021·Frontiers in Cellular Neuroscience·Janani S IyerKonstantina M Stankovic

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Methods Mentioned

BETA
scanning
transmission electron microscopy
cochlear sections
confocal microscopy
co-immunoprecipitation

Software Mentioned

Imaris
SR
SIM
NIS Element
ZEN

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