GJB6

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Gap junction protein, beta 6, 30kDa
Identifiers
Symbols GJB6 ; CX30; DFNA3; DFNA3B; DFNB1B; ECTD2; ED2; EDH; HED; HED2
External IDs OMIM604418 MGI107588 HomoloGene4936 IUPHAR: Cx30 GeneCards: GJB6 Gene
Orthologs
Species Human Mouse
Entrez 10804 14623
Ensembl ENSG00000121742 ENSMUSG00000040055
UniProt O95452 P70689
RefSeq (mRNA) NM_001110219 NM_001010937
RefSeq (protein) NP_001103689 NP_001010937
Location (UCSC) Chr 13:
20.8 – 20.81 Mb
Chr 14:
57.12 – 57.13 Mb
PubMed search [1] [2]

Gap junction beta-6 protein (GJB6), also known as connexin 30 (Cx30) — is a protein that in humans is encoded by the GJB6 gene.[1][2][3] Connexin 30 (Cx30) is one of several gap junction proteins expressed in the inner ear.[4] Mutations in gap junction genes have been found to lead to both syndromic and nonsyndromic deafness.[5]

Function[edit]

The connexin gene family codes for the protein subunits of gap junction channels that mediate direct diffusion of ions and metabolites between the cytoplasm of adjacent cells. Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are expressed in a cell type-specific manner with overlapping specificity. The gap junction channels have unique properties depending on the type of connexins constituting the channel.[supplied by OMIM][3]

Connexin 30 is prevalent in the two distinct gap junction systems found in the cochlea: the epithelial cell gap junction network, which couple non-sensory epithelial cells, and the connective tissue gap junction network, which couple connective tissue cells. Gap junctions serve the important purpose of recycling potassium ions that pass through hair cells during mechanotransduction back to the endolymph.[6]

Connexin 30 has been found to be co-localized with connexin 26.[7] Cx30 and Cx26 have also been found to form heteromeric and heterotypic channels. The biochemical properties and channel permeabilities of these more complex channels differ from homotypic Cx30 or Cx26 channels.[8] Overexpression of Cx30 in Cx30 null mice restored Cx26 expression and normal gap junction channel functioning and calcium signaling, but it is described that Cx26 expression is altered in Cx30 null mice. The researchers hypothesized that co-regulation of Cx26 and Cx30 is dependent on phospholipase C signaling and the NF-κB pathway.[9]

The cochlea contains two cell types, auditory hair cells for mechanotransduction and supporting cells. Gap junction channels are only found between cochlear supporting cells.[10] While gap junctions in the inner ear are critically involved in potassium recycling to the endolymph, connexin expression in the supporting cells surrounding the organ of Corti have been found to support epithelial tissue lesion repair following loss of sensory hair cells. An experiment with Cx30 null mice found deficits in lesion closure and repair of the organ of Corti following hair cell loss, suggesting that Cx30 has a role in regulating lesion repair response.[11]

Clinical Significance[edit]

Auditory[edit]

Connexin 26 and connexin 30 are commonly accepted to be the predominant gap junction proteins in the cochlea. Genetic knockout experiments in mice has shown that knockout of either Cx26 or Cx30 produces deafness.[12][13] However, recent research suggests that Cx30 knockout produces deafness due to subsequent downregulation of Cx26, and one mouse study found that a Cx30 mutation that preserves half of Cx26 expression found in normal Cx30 mice resulted in unimpaired hearing.[14] The lessened severity of Cx30 knockout in comparison to Cx26 knockout is supported by a study examining the time course and patterns of hair cell degeneration in the cochlea. Cx26 null mice displayed more rapid and widespread cell death than Cx30 null mice. The percent hair cell loss was less widespread and frequent in the cochleas of Cx30 null mice.[15]

References[edit]

  1. ^ Grifa A, Wagner CA, D'Ambrosio L, Melchionda S, Bernardi F, Lopez-Bigas N, Rabionet R, Arbones M, Monica MD, Estivill X, Zelante L, Lang F, Gasparini P (Sep 1999). "Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus". Nat Genet 23 (1): 16–8. doi:10.1038/12612. PMID 10471490. 
  2. ^ Kibar Z, Der Kaloustian VM, Brais B, Hani V, Fraser FC, Rouleau GA (Oct 1996). "The gene responsible for Clouston hidrotic ectodermal dysplasia maps to the pericentromeric region of chromosome 13q". Hum Mol Genet 5 (4): 543–7. doi:10.1093/hmg/5.4.543. PMID 8845850. 
  3. ^ a b "Entrez Gene: GJB6 gap junction protein, beta 6". 
  4. ^ Zhao, H. -B.; Kikuchi, T.; Ngezahayo, A.; White, T. W. (2006). "Gap Junctions and Cochlear Homeostasis". Journal of Membrane Biology 209 (2–3): 177–186. doi:10.1007/s00232-005-0832-x. PMC 1609193. PMID 16773501.  edit
  5. ^ Erbe, C. B.; Harris, K. C.; Runge-Samuelson, C. L.; Flanary, V. A.; Wackym, P. A. (2004). "Connexin 26 and Connexin 30 Mutations in Children with Nonsyndromic Hearing Loss". The Laryngoscope 114 (4): 607–611. doi:10.1097/00005537-200404000-00003. PMID 15064611.  edit
  6. ^ Kikuchi, T.; Kimura, R. S.; Paul, D. L.; Takasaka, T.; Adams, J. C. (2000). "Gap junction systems in the mammalian cochlea". Brain research. Brain research reviews 32 (1): 163–166. doi:10.1016/S0165-0173(99)00076-4. PMID 10751665.  edit
  7. ^ Lautermann, J.; Ten Cate, W. J.; Altenhoff, P.; Grümmer, R.; Traub, O.; Frank, H.; Jahnke, K.; Winterhager, E. (1998). "Expression of the gap-junction connexins 26 and 30 in the rat cochlea". Cell and tissue research 294 (3): 415–420. doi:10.1007/s004410051192. PMID 9799458.  edit
  8. ^ Yum, S. W.; Zhang, J.; Valiunas, V.; Kanaporis, G.; Brink, P. R.; White, T. W.; Scherer, S. S. (2007). "Human connexin26 and connexin30 form functional heteromeric and heterotypic channels". AJP: Cell Physiology 293 (3): C1032–C1048. doi:10.1152/ajpcell.00011.2007. PMID 17615163.  edit
  9. ^ Ortolano, S.; Di Pasquale, G.; Crispino, G.; Anselmi, F.; Mammano, F.; Chiorini, J. A. (2008). "Coordinated control of connexin 26 and connexin 30 at the regulatory and functional level in the inner ear". Proceedings of the National Academy of Sciences 105 (48): 18776–18781. doi:10.1073/pnas.0800831105. PMC 2596232. PMID 19047647.  edit
  10. ^ Kikuchi, T.; Kimura, R. S.; Paul, D. L.; Adams, J. C. (1995). "Gap junctions in the rat cochlea: Immunohistochemical and ultrastructural analysis". Anatomy and embryology 191 (2): 101–118. doi:10.1007/BF00186783. PMID 7726389.  edit
  11. ^ Forge, A.; Jagger, D. J.; Kelly, J. J.; Taylor, R. R. (2013). "Connexin30 mediated intercellular communication plays an essential role in epithelial repair in the cochlea". Journal of Cell Science. doi:10.1242/jcs.125476. PMID 23424196.  edit
  12. ^ Teubner, B.; Michel, V.; Pesch, J.; Lautermann, J.; Cohen-Salmon, M.; Söhl, G.; Jahnke, K.; Winterhager, E.; Herberhold, C.; Hardelin, J. P.; Petit, C.; Willecke, K. (2003). "Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential". Human molecular genetics 12 (1): 13–21. doi:10.1093/hmg/ddg001. PMID 12490528.  edit
  13. ^ Kudo, T.; Kure, S.; Ikeda, K.; Xia, A. P.; Katori, Y.; Suzuki, M.; Kojima, K.; Ichinohe, A.; Suzuki, Y.; Aoki, Y.; Kobayashi, T.; Matsubara, Y. (2003). "Transgenic expression of a dominant-negative connexin26 causes degeneration of the organ of Corti and non-syndromic deafness". Human molecular genetics 12 (9): 995–1004. doi:10.1093/hmg/ddg116. PMID 12700168.  edit
  14. ^ Boulay, A. -C.; Del Castillo, F. J.; Giraudet, F.; Hamard, G.; Giaume, C.; Petit, C.; Avan, P.; Cohen-Salmon, M. (2013). "Hearing is Normal without Connexin30". Journal of Neuroscience 33 (2): 430–434. doi:10.1523/JNEUROSCI.4240-12.2013. PMID 23303923.  edit
  15. ^ Sun, Y.; Tang, W.; Chang, Q.; Wang, Y.; Kong, W.; Lin, X. (2009). "Connexin30 null and conditional connexin26 null mice display distinct pattern and time course of cellular degeneration in the cochlea". The Journal of Comparative Neurology 516 (6): 569–579. doi:10.1002/cne.22117. PMC 2846422. PMID 19673007.  edit

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