Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: Insights into syndromic hearing loss

Helmuth A. Sanchez, Vytautas Verselis

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Mutation of the GJB2 gene, which encodes the connexin 26 (Cx26) gap junction (GJ) protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs), have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction.

Original languageEnglish (US)
Article number354
JournalFrontiers in Cellular Neuroscience
Volume8
Issue numberOctober
DOIs
StatePublished - Oct 27 2014

Fingerprint

Hearing Loss
Deafness
Cochlea
Mutation
Connexins
Sensorineural Hearing Loss
Gap Junctions
Ion Channels
Epithelial Cells
Genotype
Cell Membrane
Keratitis, Ichthyosis, and Deafness (KID) Syndrome
Connexin 26
Phenotype
Skin
Genes

Keywords

  • Calcium
  • Cochlea
  • Connexin
  • Deafness
  • Gating
  • Hemichannel
  • Permeability

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome : Insights into syndromic hearing loss. / Sanchez, Helmuth A.; Verselis, Vytautas.

In: Frontiers in Cellular Neuroscience, Vol. 8, No. October, 354, 27.10.2014.

Research output: Contribution to journalArticle

@article{f86936f7f2e54f57842f2ee28fac0e48,
title = "Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: Insights into syndromic hearing loss",
abstract = "Mutation of the GJB2 gene, which encodes the connexin 26 (Cx26) gap junction (GJ) protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs), have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction.",
keywords = "Calcium, Cochlea, Connexin, Deafness, Gating, Hemichannel, Permeability",
author = "Sanchez, {Helmuth A.} and Vytautas Verselis",
year = "2014",
month = "10",
day = "27",
doi = "10.3389/fncel.2014.00354",
language = "English (US)",
volume = "8",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Research Foundation",
number = "October",

}

TY - JOUR

T1 - Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome

T2 - Insights into syndromic hearing loss

AU - Sanchez, Helmuth A.

AU - Verselis, Vytautas

PY - 2014/10/27

Y1 - 2014/10/27

N2 - Mutation of the GJB2 gene, which encodes the connexin 26 (Cx26) gap junction (GJ) protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs), have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction.

AB - Mutation of the GJB2 gene, which encodes the connexin 26 (Cx26) gap junction (GJ) protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs), have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction.

KW - Calcium

KW - Cochlea

KW - Connexin

KW - Deafness

KW - Gating

KW - Hemichannel

KW - Permeability

UR - http://www.scopus.com/inward/record.url?scp=84908371596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908371596&partnerID=8YFLogxK

U2 - 10.3389/fncel.2014.00354

DO - 10.3389/fncel.2014.00354

M3 - Article

AN - SCOPUS:84908371596

VL - 8

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

IS - October

M1 - 354

ER -