XB-ART-46961
Biochim Biophys Acta
2012 Aug 01;18188:2014-9. doi: 10.1016/j.bbamem.2011.09.003.
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Pathological hemichannels associated with human Cx26 mutations causing Keratitis-Ichthyosis-Deafness syndrome.
Levit NA
,
Mese G
,
Basaly MG
,
White TW
.
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Connexin (Cx) proteins form intercellular gap junction channels by first assembling into single membrane hemichannels that then dock to connect the cytoplasm of two adjacent cells. Gap junctions are highly specialized structures that allow the direct passage of small molecules between cells to maintain tissue homeostasis. Functional activity of nonjunctional hemichannels has now been shown in several experimental systems. Hemichannels may constitute an important diffusional exchange pathway with the extracellular space, but the extent of their normal physiological role is currently unknown. Aberrant hemichannel activity has been linked to mutations of connexin proteins involved in genetic diseases. Here, we review a proposed role for hemichannels in the pathogenesis of Keratitis-Ichthyosis-Deafness (KID) syndrome associated with connexin26 (Cx26) mutations. Continued functional evaluation of mutated hemichannels linked to human hereditary disorders may provide additional insights into the mechanisms governing their regulation in normal physiology and dysregulation in disease. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
???displayArticle.pubmedLink??? 21933663
???displayArticle.pmcLink??? PMC3245810
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???displayArticle.grants??? [+]
R01 AR059505 NIAMS NIH HHS , R01 AR059505-01 NIAMS NIH HHS , R01 AR059505-02 NIAMS NIH HHS , R01 AR059505-03 NIAMS NIH HHS , T32 GM008444 NIGMS NIH HHS
Species referenced: Xenopus
Genes referenced: gjb2 kif22
References [+] :
Anand,
The role of gap junctions in health and disease.
2005, Pubmed
Anand, The role of gap junctions in health and disease. 2005, Pubmed
Arita, A novel N14Y mutation in Connexin26 in keratitis-ichthyosis-deafness syndrome: analyses of altered gap junctional communication and molecular structure of N terminus of mutated Connexin26. 2006, Pubmed
Bai, Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB). 2006, Pubmed
Bakirtzis, Targeted epidermal expression of mutant Connexin 26(D66H) mimics true Vohwinkel syndrome and provides a model for the pathogenesis of dominant connexin disorders. 2003, Pubmed
Beahm, Hemichannel and junctional properties of connexin 50. 2002, Pubmed , Xenbase
Beltramello, Impaired permeability to Ins(1,4,5)P3 in a mutant connexin underlies recessive hereditary deafness. 2005, Pubmed
Bennett, New roles for astrocytes: gap junction hemichannels have something to communicate. 2003, Pubmed
Bevans, Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules. 1998, Pubmed
Bruzzone, Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness. 2003, Pubmed , Xenbase
Bukauskas, Gap junction channel gating. 2004, Pubmed
D'Adamo, Does epidermal thickening explain GJB2 high carrier frequency and heterozygote advantage? 2009, Pubmed
DeVries, Modulation of an electrical synapse between solitary pairs of catfish horizontal cells by dopamine and second messengers. 1989, Pubmed
DeVries, Hemi-gap-junction channels in solitary horizontal cells of the catfish retina. 1992, Pubmed
Di, Connexin 26 expression and mutation analysis in epidermal disease. 2001, Pubmed
Ebihara, Properties of a nonjunctional current expressed from a rat connexin46 cDNA in Xenopus oocytes. 1993, Pubmed , Xenbase
Eskandari, Inhibition of gap junction hemichannels by chloride channel blockers. 2002, Pubmed , Xenbase
Essenfelder, Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity. 2004, Pubmed , Xenbase
Evans, The gap junction cellular internet: connexin hemichannels enter the signalling limelight. 2006, Pubmed
Gerido, Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness. 2007, Pubmed , Xenbase
Gerido, Connexin disorders of the ear, skin, and lens. 2004, Pubmed
Giepmans, Interaction of c-Src with gap junction protein connexin-43. Role in the regulation of cell-cell communication. 2001, Pubmed
Goliger, Wounding alters epidermal connexin expression and gap junction-mediated intercellular communication. 1995, Pubmed
Goodenough, Bulk isolation of mouse hepatocyte gap junctions. Characterization of the principal protein, connexin. 1974, Pubmed
Goodenough, Beyond the gap: functions of unpaired connexon channels. 2003, Pubmed
Griffith, Cochleosaccular dysplasia associated with a connexin 26 mutation in keratitis-ichthyosis-deafness syndrome. 2006, Pubmed
Harris, Emerging issues of connexin channels: biophysics fills the gap. 2001, Pubmed
Janecke, GJB2 mutations in keratitis-ichthyosis-deafness syndrome including its fatal form. 2005, Pubmed
Jonard, A familial case of Keratitis-Ichthyosis-Deafness (KID) syndrome with the GJB2 mutation G45E. 2008, Pubmed
KANNO, LOW-RESISTANCE COUPLING BETWEEN GLAND CELLS. SOME OBSERVATIONS ON INTERCELLULAR CONTACT MEMBRANES AND INTERCELLULAR SPACE. 1964, Pubmed
Kam, Patterns of junctional communication in skin. 1986, Pubmed
Kelsell, Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family. 2000, Pubmed
Labarthe, Upregulation of connexin 26 between keratinocytes of psoriatic lesions. 1998, Pubmed
Lai-Cheong, Genetic diseases of junctions. 2007, Pubmed
Lawrence, Transmission of hormonal stimulation by cell-to-cell communication. 1978, Pubmed
Lee, Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes. 2009, Pubmed , Xenbase
Lee, Connexin-26 mutations in deafness and skin disease. 2009, Pubmed
Lerer, Contribution of connexin 26 mutations to nonsyndromic deafness in Ashkenazi patients and the variable phenotypic effect of the mutation 167delT. 2000, Pubmed
Liang, Severe neuropathy with leaky connexin32 hemichannels. 2005, Pubmed , Xenbase
Locke, Isoelectric points and post-translational modifications of connexin26 and connexin32. 2006, Pubmed
Lucke, Upregulation of connexin 26 is a feature of keratinocyte differentiation in hyperproliferative epidermis, vaginal epithelium, and buccal epithelium. 1999, Pubmed
Maeda, Structure of the connexin 26 gap junction channel at 3.5 A resolution. 2009, Pubmed
Malchow, Evidence for hemi-gap junctional channels in isolated horizontal cells of the skate retina. 1993, Pubmed
Martínez, Gap-junction channels dysfunction in deafness and hearing loss. 2009, Pubmed
Mazereeuw-Hautier, Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. 2007, Pubmed
Meyer, Selection for deafness? 2002, Pubmed
Meşe, Gap junctions: basic structure and function. 2007, Pubmed
Meşe, Connexin26 deafness associated mutations show altered permeability to large cationic molecules. 2008, Pubmed
Montgomery, A novel connexin 26 gene mutation associated with features of the keratitis-ichthyosis-deafness syndrome and the follicular occlusion triad. 2004, Pubmed , Xenbase
Paul, Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes. 1991, Pubmed , Xenbase
Petit, From deafness genes to hearing mechanisms: harmony and counterpoint. 2006, Pubmed
Petit, Molecular genetics of hearing loss. 2001, Pubmed
ROBERTSON, THE OCCURRENCE OF A SUBUNIT PATTERN IN THE UNIT MEMBRANES OF CLUB ENDINGS IN MAUTHNER CELL SYNAPSES IN GOLDFISH BRAINS. 1963, Pubmed
Retamal, S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: induction by oxidant stress and reversal by reducing agents. 2006, Pubmed
Revel, Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. 1967, Pubmed
Richard, Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma. 1998, Pubmed
Richard, Connexin disorders of the skin. 2005, Pubmed
Richard, Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. 2002, Pubmed
Rivas, Identification of aberrantly regulated genes in diseased skin using the cDNA differential display technique. 1997, Pubmed
Rouan, trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation. 2001, Pubmed , Xenbase
Salomon, Cell-to-cell communication within intact human skin. 1988, Pubmed
Sawey, Perturbation in connexin 43 and connexin 26 gap-junction expression in mouse skin hyperplasia and neoplasia. 1996, Pubmed
Sbidian, Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form. 2010, Pubmed
Schalper, Dysfunctions of the diffusional membrane pathways mediated by hemichannels in inherited and acquired human diseases. 2009, Pubmed
Solan, Connexin43 phosphorylation: structural changes and biological effects. 2009, Pubmed
Spray, Prospects for rational development of pharmacological gap junction channel blockers. 2002, Pubmed
Srinivas, Closure of gap junction channels by arylaminobenzoates. 2003, Pubmed
Stong, A novel mechanism for connexin 26 mutation linked deafness: cell death caused by leaky gap junction hemichannels. 2006, Pubmed
Stout, Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. 2002, Pubmed
Stout, Connexins: functions without junctions. 2004, Pubmed
Sun, Cochlear gap junctions coassembled from Cx26 and 30 show faster intercellular Ca2+ signaling than homomeric counterparts. 2005, Pubmed
Sáez, Connexin-based gap junction hemichannels: gating mechanisms. 2005, Pubmed
Sáez, Cell membrane permeabilization via connexin hemichannels in living and dying cells. 2010, Pubmed
Sánchez, Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome. 2010, Pubmed , Xenbase
Tao, 2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. 2007, Pubmed
Valiunas, Biophysical properties of connexin-45 gap junction hemichannels studied in vertebrate cells. 2002, Pubmed
Veenstra, Size and selectivity of gap junction channels formed from different connexins. 1996, Pubmed
Verselis, Divalent cations regulate connexin hemichannels by modulating intrinsic voltage-dependent gating. 2008, Pubmed , Xenbase
Wang, Functional analysis of connexin-26 mutants associated with hereditary recessive deafness. 2003, Pubmed
Wei, Connexins and cell signaling in development and disease. 2004, Pubmed
White, Genetic diseases and gene knockouts reveal diverse connexin functions. 1999, Pubmed
White, Functional characteristics of skate connexin35, a member of the gamma subfamily of connexins expressed in the vertebrate retina. 1999, Pubmed , Xenbase
Zhang, Gap junction-mediated intercellular biochemical coupling in cochlear supporting cells is required for normal cochlear functions. 2005, Pubmed
Zhao, Gap junctions and cochlear homeostasis. 2006, Pubmed
de Zwart-Storm, Molecular analysis of connexin26 asparagine14 mutations associated with syndromic skin phenotypes. 2011, Pubmed