Keratitis-ichthyosis-deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

Journal of Investigative Dermatology

Volumn 135, Issue 5, 2015, Pages 1338-1347

  García, Isaac E ^a   Maripillán, Jaime ^a   Jara, Oscar ^a   Ceriani, Ricardo ^a   Palacios Muñoz, Angelina ^a   Ramachandran, Jayalakshmi ^b   Olivero, Pablo ^c   Perez Acle, Tomas ^a,d   González, Carlos ^a   Sáez, Juan C ^a,e   Contreras, Jorge E ^b   Martínez, Agustín D ^a  

^a Centro Interdisciplinario de Neurociencias de Valparaíso   (Chile)

^b RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^c UNIVERSIDAD DE VALPARAÍSO   (Chile)

^d Fundacion Ciencia para la Vida   (Chile)

^e PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALCIUM; CONNEXIN 26; CONNEXIN 30; CONNEXIN 43; GAP JUNCTION PROTEIN; ION CHANNEL;

ARTICLE; AUTOSOMAL DOMINANT INHERITANCE; CELL MEMBRANE PERMEABILITY; CELLULAR DISTRIBUTION; DISEASE ASSOCIATION; GAP JUNCTION; GENE MUTATION; GENETIC TRANSFECTION; HEARING IMPAIRMENT; HELA CELL LINE; HETEROLOGOUS EXPRESSION; HUMAN; HUMAN TISSUE; ICHTHYOSIS; IMMUNOBLOTTING; KERATITIS; KERATITIS ICHTHYOSIS DEAFNESS SYNDROME; MOLECULAR CLONING; OLIGOMERIZATION; PHENOTYPE; PRIORITY JOURNAL; SEDIMENTATION RATE; SUCROSE GRADIENT; WILD TYPE; GENETICS; GENOTYPE; METABOLISM; MUTATION; PATHOPHYSIOLOGY; PHYSIOLOGY;

ADENOSINE TRIPHOSPHATE; CALCIUM; CELL MEMBRANE PERMEABILITY; CONNEXIN 43; CONNEXINS; DEAFNESS; GAP JUNCTIONS; GENOTYPE; HELA CELLS; HUMANS; ICHTHYOSIS; ION CHANNELS; KERATITIS; MUTATION; PHENOTYPE;

EID: 84928417149     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/jid.2015.20     Document Type: Article

References (48)

1. Anselmi F, Hernandez VH, Crispino G et al. (2008) ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear. Proc Natl Acad Sci USA 105:18770-5
2. Arita K, Akiyama M, Aizawa T et al. (2006) 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. Am J Pathol 169:416-23
3. Bargiello TA, Tang Q, Oh S et al. (2012) Voltage-dependent conformational changes in connexin channels. Biochim Biophys Acta 1818:1807-22
4. Barrio LC, Suchyna T, Bargiello T et al. (1991) Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage. Proc Natl Acad Sci USA 88:8410-4
5. Berthoud VM, Montegna EA, Atal N et al. (2001) Heteromeric connexons formed by the lens connexins, connexin43 and connexin56. Eur J Cell Biol 80:11-9
6. Beyer EC, Gemel J, Martínez A et al. (2001) Heteromeric mixing of connexins: compatibility of partners and functional consequences. Cell Commun Adhes 8:199-204
7. Caceres-Rios H, Tamayo-Sanchez L, Duran-Mckinster C et al. (1996) Keratitis, ichthyosis, and deafness (KID syndrome): review of the literature and proposal of a new terminology. Pediatr Dermatol 13:105-13
8. Contreras JE, Sáez JC, Bukauskas FF et al. (2003) Gating and regulation of connexin 43 (Cx43) hemichannels. Proc Natl Acad Sci USA 100:11388-93
9. Contreras JE, Sánchez HA, Eugenín EA et al. (2002) Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc Natl Acad Sci USA 99:495-500
10. Denda M, Inoue K, Fuziwara S et al. (2002) P2X purinergic receptor antagonist accelerates skin barrier repair and prevents epidermal hyperplasia induced by skin barrier disruption. J Invest Dermatol 119:1034-40
11. Djalilian AR, McGaughey D, Patel S et al. (2006) Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response. J Invest Dermatol 116:1243-53
12. Fiori MC, Figueroa V, Zoghbi ME et al. (2012) Permeation of calcium through purified connexin 26 hemichannels. J Biol Chem 287:40826-34
13. Forge A, Becker D, Casalotti S et al. (2003) Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals. J Comp Neurol 467:207-31
14. Gemel J, Valiunas V, Brink PR et al. (2004) Connexin43 and connexin26 form gap junctions, but not heteromeric channels in co-expressing cells. J Cell Sci 117:2469-80
15. Gerido DA, DeRosa AM, Richard G et al. (2007) Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness. Am J Physiol Cell Physiol 293:C337-45
16. Goliger JA, Paul DL (1994) Expression of gap junction proteins Cx26, Cx31.1, Cx37, and Cx43 in developing and mature rat epidermis. Dev Dyn 200: 1-13
17. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440-50
18. Hansen DB, Braunstein TH, Nielsen MS et al. (2014) Distinct permeation profiles of the connexin 30 and 43 hemichannels. FEBS Lett 588:1446-57
19. Jacquemond V (1997) Indo-1 fluorescence signals elicited by membrane depolarization in enzymatically isolated mouse skeletal muscle fibers. Biophys J 73:920-8
20. Jara O, Acuna R, Garcia IE et al. (2012) Critical role of the first transmembrane domain of Cx26 in regulating oligomerization and function. Mol Biol Cell 23:3299-311
21. Kelsell DP, Wilgoss AL, Richard G et al. (2000) Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family. Eur J Hum Genet 8:141-4
22. Kwon T, Harris AL, Rossi A et al. (2011) Molecular dynamics simulations of the Cx26 hemichannel: evaluation of structural models with Brownian dynamics. J Gen Physiol 138:475-93
23. Kyle JW, Minogue PJ, Thomas BC et al. (2008) An intact connexin N-terminus is required for function but not gap junction formation. J Cell Sci 121:2744-50
24. Lagree V, Brunschwig K, Lopez P et al. (2003) Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43. J Cell Sci 116:3189-201
25. Lee JR, Derosa AM, White TW(2009) Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes. J Invest Dermatol 129:870-8
26. Levit NA, Mese G, Basaly MG et al. (2012) Pathological hemichannels associated with human Cx26 mutations causing Keratitis-Ichthyosis-Deafness syndrome. Biochim Biophys Acta 1818:2014-9
27. Lopez W, Gonzalez J, Liu Y et al. (2013a) Insights on the mechanisms of Ca(2+) regulation of connexin26 hemichannels revealed by human pathogenic mutations (D50N/Y). J Gen Physiol 142:23-35
28. Lopez W, Liu Y, Harris AL et al. (2013b) Divalent regulation and intersubunit interactions of human Connexin26 (Cx26) hemichannels. Channels 8:1-4
29. Maeda S, Nakagawa S, Suga M et al. (2009) Structure of the connexin 26 gap junction channel at 3.5A resolution. Nature 458:597-602
30. Martínez AD, Acuña R, Figueroa V et al. (2009) Gap-junction channels dysfunction in deafness and hearing loss. Antioxid Redox Signal 11:309-22
31. Martinez AD, Hayrapetyan V, Moreno AP et al. (2002) Connexin43 and connexin45 form heteromeric gap junction channels in which individual components determine permeability and regulation. Circ Res 90:1100-7
32. Martínez AD, Maripillan J, Acuna R et al. (2011) Different domains are critical for oligomerization compatibility of different connexins. Biochem J 436:35-43
33. Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J et al. (2007) Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol 156: 1015-9
34. Richard G (2000) Connexins: a connection with the skin. Exp Dermatol 9: 77-96
35. Richard G, Rouan F, Willoughby CE et al. (2002) Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis- deafness syndrome. Am J Hum Genet 70:1341-8
36. Risek B, Klier FG, Gilula NB (1992) Multiple gap junction genes are utilized during rat skin and hair development. Development 116:639-51
37. Rouan F, White TW, Brown N et al. (2001) trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation. J Cell Sci 114:2105-13
38. Sáez JC, Retamal MA, Basilio D et al. (2005) Connexin-based gap junction hemichannels: gating mechanisms. Biochim Biophys Acta 1711: 215-24
39. Sáez JC, Schalper KA, Retamal MA et al. (2010) Cell membrane permeabilization via connexin hemichannels in living and dying cells. Exp Cell Res 316:2377-89
40. Salomon D, Masgrau E, Vischer S et al. (1994) Topography of mammalian connexins in human skin. J Invest Dermatol 103:240-7
41. Sánchez HA, Mese G, Srinivas M et al. (2010) Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome. J Gen Physiol 136:47-62
42. Segretain D, Falk MM (2004) Regulation of connexin biosynthesis, assembly, gap junction formation, and removal. Biochim Biophys Acta 1662:3-21
43. Stout C, Goodenough DA, Paul DL (2004) Connexins: functions without junctions. Curr Opin Cell Biol 16:507-12
44. Stout CE, Costantin JL, Naus CC et al. (2002) Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem 277:10482-8
45. Verrall S, Hall ZW (1992) The N-terminal domains of acetylcholine receptor subunits contain recognition signals for the initial steps of receptor assembly. Cell 68:23-31
46. Verselis VK, Ginter CS, Bargiello TA (1994) Opposite voltage gating polarities of two closely related connexins. Nature 368:348-51
47. White TW, Deans MR, O'Brien J et al. (1999) Functional characteristics of skate connexin35, a member of the gamma subfamily of connexins expressed in the vertebrate retina. Eur J Neurosci 11:1883-90
48. Wiszniewski L, Limat A, Saurat JH et al. (2000) Differential expression of connexins during stratification of human keratinocytes. J Invest Dermatol 115:278-85