Dominant Cx26 mutants associated with hearing loss have dominant-negative effects on wild type Cx26

Molecular and Cellular Neuroscience

Volumn 47, Issue 2, 2011, Pages 71-78

  Zhang, Junxian ^a   Scherer, Steven S ^b   Yum, Sabrina W ^a,b  

^a Childrens Hospital of Philadelphia   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Cochlea; Disease mechanism; Dye transfer; FRAP; Gap junctions; Hearing; Immunoprecipitation

Indexed keywords

CALCEIN; CONNEXIN 26; GAP JUNCTION PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COCHLEA; CONTROLLED STUDY; FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING; GAP JUNCTION; GENE MUTATION; GENETIC TRANSFECTION; HEARING LOSS; HELA CELL; HUMAN; HUMAN TISSUE; IMMUNOPRECIPITATION; MOUSE; NONHUMAN; PALMOPLANTAR KERATODERMA; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; WILD TYPE;

ANIMALS; CONNEXINS; FLUORESCEINS; GAP JUNCTIONS; GENES, DOMINANT; HEARING LOSS; HELA CELLS; HUMANS; KERATODERMA, PALMOPLANTAR; MUTATION;

EID: 79955977354     PISSN: 10447431     EISSN: 10959327     Source Type: Journal    
DOI: 10.1016/j.mcn.2010.10.002     Document Type: Article

References (49)

1. Ahmad S., Chen S.P., Sun J.J., Lin X. Connexins 26 and 30 are co-assembled to form gap junctions in the cochlea of mice. Biochem. Biophys. Res. Commun. 2003, 307:362-368.
2. Bakirtzis G., Choudhry R., Aasen T., Shore L., Brown K., Bryson S., Forrow S., Tetley L., Finbow M., Greenhalgh D., Hodgins M. Targeted epidermal expression of mutant connexin 26(D66H) mimics true Vohwinkel syndrome and provides a model for the pathogenesis of dominant connexin disorders. Hum. Mol. Genet. 2003, 12:1737-1744.
3. Beltramello M., Piazza V., Bukauskas F.F., Pozzan T., Mammano F. Impaired permeability to Ins(1, 4, 5)P3 in a mutant connexin underlies recessive hereditary deafness. Nat. Cell Biol. 2005, 7:63-69.
4. Bruzzone R., White T.W., Paul D.L. Connections with connexins: the molecular basis of direct intercellular signaling. Eur. J. Biochem. 1996, 238:1-27.
5. Bukauskas F.F., Bukauskiene A., Bennett M.V., Verselis V.K. Gating properties of gap junction channels assembled from connexin43 and connexin43 fused with green fluorescent protein. Biophys. J. 2001, 81:137-152.
6. Chang Q., Tang W., Ahmad S., Zhou B., Lin X. Gap junction mediated intercellular metabolite transfer in the cochlea is compromised in connexin30 null mice. PLoS ONE 2008, 3:e4088.
7. Chen Y.Y., Deng Y.Q., Bao X.Y., Reuss L., Altenberg G.A. Mechanism of the defect in gap-junctional communication by expression of a connexin 26 mutant associated with dominant deafness. FASEB J. 2005, 19:U587-U602.
8. Cohen-Salmon M., Ott T., Michel V., Hardelin J.P., Perfettini I., Eybalin M., Wu T., Marcus D.C., Wangemann P., Willecke K., Petit C. Targeted ablation of connexin26 in the inner ear epithelial gap junction network causes hearing impairment and cell death. Curr. Biol. 2002, 12:1106-1111.
9. Common J.E.A., Di W.L., Davies D., Kelsell D.P. Further evidence for heterozygote advantage of GJB2 deafness mutations: a link with cell survival. J. Med. Genet. 2004, 41:573-575.
10. Elfgang C., Eckert R., Lichternberg-Frate H., Butterweck A., Traub O., Klein R.A., Hulser D.F., Willecke K. Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. J. Cell Biol. 1995, 129:805-817.
11. Estivill X., Fortina P., Surrey S., Rabionet R., Melchionda S., D'Agruma L., Mansfield E., Rappaport E., Govea N., Mila M., Zelante L., Gasparini P. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet 1998, 351:394-398.
12. Forge A., Becker D., Casalotti S., Edwards J., Marziano N., Nickel R. Connexins and gap junctions in the inner ear. Audiol. Neuro Otol. 2002, 7:141-145.
13. Gemel J., Valiunas V., Brink P.R., Beyer E.C. Connexin43 and connexin26 form gap junctions, but not heteromeric channels in co-expressing cells. J. Cell Sci. 2004, 117:2469-2480.
14. Gerido D.A., DeRosa A.M., Richard G., White T.W. Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness. Am. J. Physiol. 2007, 293:C337-C345.
15. Grifa A., Wagner C.A., D'Ambrosio L., Melchionda S., Bernardi F., Lopez-Bigas N., Rabionet R., Arbones M., Della Monica M., Estivill X., Zelante L., Lang F., Gasparini P. Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat. Genet. 1999, 23:16-18.
16. Harris A.L. Emerging issues of connexin channels: biophysics fills the gap. Q. Rev. Biophys. 2001, 34:325-472.
17. Inoshita A., Iizuka T., Okamura H.O., Minekawa A., Kojima K., Furukawa M., Kusunoki T., Ikeda K. Postnatal development of the organ of Corti in dominant-negative Gjb2 transgenic mice. Neuroscience 2008, 156:1039-1047.
18. Jagger D.J., Forge A. Compartmentalized and signal-selective gap junctional coupling in the hearing cochlea. J. Neurosci. 2006, 26:1260-1268.
19. Kelsell D.P., Dunlop J., Stevens H.P., Lench N.J., Liang J.N., Parry G., Mueller R.F., Leigh I.M. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 1997, 387:80-83.
20. Kikuchi T., Kimura R.S., Paul D.L., Adams J.C. Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat. Embryol. 1995, 191:101-118.
21. Kumar N.M., Gilula N.B. The gap junction communication channel. Cell 1996, 84:381-389.
22. Lautermann J., tenCate W.J.F., Altenhoff P., Grummer R., Traub O., Frank H.G., Jahnke K., Winterhager E. Expression of the gap-junction connexins 26 and 30 in the rat cochlea. Cell Tissue Res. 1998, 294:415-420.
23. Lee J.R., Derosa A.M., White T.W. Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes. J. Investig. Dermatol. 2009, 129:870-878.
24. Maeda S., Nakagawa S., Suga M., Yamashita E., Oshima A., Fujiyoshi Y., Tsukihara T. Structure of the connexin 26 gap junction channel at 3.5A resolution. Nature 2009, 458:597-602.
25. Manthey D., Banach K., Desplantez T., Lee C.G., Kozak C.A., Traub O., Weingart R., Willecke K. Intracellular domains of mouse connexin26 and -30 affect diffusional and electrical properties of gap junction channels. J. Membr. Biol. 2001, 181:137-148.
26. Marziano N.K., Casalotti S.O., Portelli A.E., Becker D.L., Forge A. Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30. Hum. Mol. Genet. 2003, 12:805-812.
27. Orthmann-Murphy J.L., Freidin M., Fischer E., Scherer S.S., Abrams C.K. Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. J. Neurosci. 2007, 27:13949-13957.
28. Oshima A., Doi T., Mitsuoka K., Maeda S., Fujiyoshi Y. Roles of Met-34, Cys-64, and Arg-75 in the assembly of human connexin 26-implication for key amino acid residues for channel formation and function. J. Biol. Chem. 2003, 278:1807-1816.
29. Piazza V., Beltramello M., Menniti M., Colao E., Malatesta P., Argento R., Chiarella G., Gallo L.V., Catalano M., Perrotti N., Mammano F., Cassandro E. Functional analysis of R75Q mutation in the gene coding for connexin 26 identified in a family with nonsyndromic hearing loss. Clin. Genet. 2005, 68:161-166.
30. Primignani P., Castorina P., Sironi F., Curcio C., Ambrosetti U., Coviello D.A. A novel dominant missense mutation-D179N-in the GJB2 gene (connexin 26) associated with non-syndromic hearing loss. Clin. Genet. 2003, 63:516-521.
31. Richard G., White T.W., Smith L.E., Bailey R.A., Compton J.G., Paul D.L., Bale S.J. Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma. Hum. Genet. 1998, 103:393-399.
32. Rouan F., White T.W., Brown N., Taylor A.V., Lucke T.W., Paul D.L., Munro C.S., Uitto J., Hodgins M.B., Richard G. Trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation. J. Cell Sci. 2001, 114:2105-2113.
33. Shurman D.L., Glazewski L., Gumpert A., Zieske J.D., Richard G. In vivo and in vitro expression of connexins in the human corneal epithelium. Investig. Ophthalmol. Vis. Sci. 2005, 46:1957-1965.
34. Stong B.C., Chang Q., Ahmad S., Lin X. A novel mechanism for connexin 26 mutation linked deafness: cell death caused by leaky gap junction hemichannels. Laryngoscope 2006, 116:2205-2210.
35. Su, C.C., Li, S.Y., Su, M.C., Chen, W.C., Yang, J.J., 2010. Mutation R184Q of connexin 26 in hearing loss patients has a dominant-negative effect on connexin 26 and connexin 30. Eur. J. Hum. Genet. 18, 1061-1064.
36. Sullivan R., Lo C.W. Expression of a connexin 43/beta-galactosidase fusion protein inhibits gap junctional communication in NIH3T3 cells. J. Cell Biol. 1995, 130:419-429.
37. Sun J.J., Ahmad S., Chen S.P., Tang W.X., Zhang Y.P., Chen P., Lin X. Cochlear gap junctions coassembled from Cx26 and 30 show faster intercellular Ca2+ signaling than homomeric counterparts. Am. J. Physiol. Cell Physiol. 2005, 288:C613-C623.
38. Teubner B., Michel V., Pesch J., Lautermann J., CohenSalmon M., Sohl G., Jahnke K., Winterhager E., Herberhold C., Hardelin J.P., Petit C., Willecke K. Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential. Hum. Mol. Genet. 2003, 12:13-21.
39. Thomas T., Telford D., Laird D.W. Functional domain mapping and selective trans-dominant effects exhibited by Cx26 disease-causing mutations. J. Biol. Chem. 2004, 279:19157-19168.
40. Thomas T., Shao Q., Laird D.W. Differentiation of organotypic epidermis in the presence of skin disease-linked dominant-negative Cx26 mutants and knockdown Cx26. J. Membr. Biol. 2007, 217:93-104.
41. Valiunas V., Manthey D., Vogel R., Willecke K., Weingart R. Biophysical properties of mouse connexin30 gap junction channels studied in transfected human HeLa cells. J. Physiol. 1999, 519(Pt 3):631-644.
42. Wang Y., Chang Q., Tang W., Sun Y., Zhou B., Li H., Lin X. Targeted connexin26 ablation arrests postnatal development of the organ of Corti. Biochem. Biophys. Res. Commun. 2009, 385:33-37.
43. Wangemann P. K+ cycling and the endocochlear potential. Hear. Res. 2002, 165:1-9.
44. White T.W., Bruzzone R. Multiple connexin proteins in single intercellular channels: connexin compatibility and functional consequences. J. Bioenerg. Biomembr. 1996, 28:339-350.
45. Willecke K., Eiberger J., Degen J., Eckardt D., Romualdi A., Guldenagel M., Deutsch U., Söhl G. Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem. 2002, 383:725-737.
46. Xia J.H., Liu C.Y., Tang B.S., Pan Q., Huang L., Dai H.P., Zhang B.R., Xie W., Hu D.X., Zheng D., Shi X.L., Wang D.A., Xia K., Yu K.P., Liao X.D., Feng Y., Yang Y.F., Xiao J.Y., Xie D.H., Huang J.Z. Mutations in the gene encoding gap junction protein ?-3 associated with autosomal dominant hearing impairment. Nat. Genet. 1998, 20:370-373.
47. Yum S.W., Zhang J., Valiunas V., Kanaporis G., Brink P.R., White T.W., Scherer S.S. Human connexin26 and connexin30 form functional heteromeric and heterotypic channels. Am. J. Physiol. 2007, 293:C1032-C1048.
48. Yum S.W., Zhang J., Scherer S.S. Dominant connexin26 mutants associated with human hearing loss have trans-dominant effects on connexin30. Neurobiol. Dis. 2010, 38:226-236.
49. Zhang Y., Tang W., Ahmad S., Sipp J.A., Chen P., Lin X. Gap junction-mediated intercellular biochemical coupling in cochlear supporting cells is required for normal cochlear functions. Proc. Natl Acad. Sci. USA 2005, 102:15201-15206.