TCDB is operated by the Saier Lab Bioinformatics Group

1.A.24 The Gap Junction-forming Connexin (Connexin) Family

Gap junctions, found in the plasma membranes of vertebrate animal cells, consist of clusters of closely packed pairs of transmembrane channels, the connexons, through which small molecules diffuse between neighboring cells (Zhou and Jiang 2014). The connexons consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. The hemichannel is made of six connexin subunits (Kar et al., 2012). The properties and possible functions of unpaired connexin and pannexin hemichannels and the implications this has for a variety of events, such as cell death, glutamate release, oxidative stress, cortical spreading depression, that occur during an ischemic insult and may affect its outcome, have been reviewed (Bargiotas et al. 2009). The two connexons are docked by interdigitated, anti-parallel beta strands across the extracellular gap. The second extracellular loop guides selectivity in docking between connexons formed by different isoforms (Kovacs et al. 2007). There is considerably more sequence variability of the N-terminal portion of E2; possibly this region dictates connexon coupling.  Structure/function relationships for connexins have been reviewed (Beyer and Berthoud 2017). The roles of connexin hemichannels in normal cochlear function and in promoting hearing loss have been reviewed (Verselis 2017).

Over 15 connexin subunit isoforms are known. They vary in size between about 25 kDa and 60 kDa. They have four putative transmembrane α-helical spanners, and direct experimental evidence favors the α-helical folding of at least two of these TMSs. Connexins are similar in sequence and are designated connexins α1-8 and β1-6. Low resolution structural data are available for a gap junction membrane channel. A dodecameric channel is formed by the end-to-end docking of two hexamers, each displaying 24 TMSs (4 α-helical TMSs per connexin subunit) (Bosco et al., 2011). Gap junctional channels are parts of multiprotein complexes (Hervé et al., 2011).  Regulation of cardiovascular connexins have been reviewed (Meens et al. 2013). The proteins interacting with Cx43, the most prevalent connexin (TC# 1.A.24.1.1; the rat and human orthologs are 98 % identical), include: c-Src (TC#1.A.23.1.12; P12931), ZO-1 (8.A.24.1.9; Q07157), drebrin (TC#; DBN1; Q16643), CIP85 (TC# 8.A.87.1.5; Q96HU1) and CCN3 (8.A.87.1.6; P48745), as well as feedback between gap junctions, adherens junctions (N-cadherin and catenins) and the cytoskeleton (microtubules and actin) (Giepmans 2006).

Connexin channels have been reconstituted in unilamellar phospholipid vesicles from purified rat liver connexin 43. The vesicles were shown to be permeable to sucrose and the dye, lucifer yellow, and channel activity was reversibly inhibited by phosphorylation of connexin 43 by mitogen-activated protein (MAP) kinase. Other kinases may also effect inhibition. Gating of connexin 43 channels may therefore be regulated by phosphorylation of the connexin subunit in vivo. However, the cytoplasmic tails differ considerably in the size and amino acid sequence for different connexins and are predicted to be involved in the channel open and closed conformations. A ball and chain model for hemichannel conformational changes has been proposed for some connexins (e.g., Cx43) with large cytoplasmic tails (Liu et al., 2006). The tail folds into a ball or 'gating particle' and binds to the cytoplasmic loop domain, leading to channel closure (Liu et al., 2006).

Different connexins may exhibit differing specificities for solutes. For example, adenosine passed about 12-fold better through channels formed by Cx32 while AMP and ADP passed about 8-fold better, and ATP greater than 300-fold better, through channels formed by Cx43. Thus, addition of phosphate to adenosine appears to shift its relative permeability from channels formed by Cx32 to channels formed by Cx43. This may have functional consequence because the energy status of a cell could be controlled via connexin expression and channel formation (Goldberg et al., 2002).

There are about 20 isoforms of connexin proteins, each forming channels with distinct channel properties (Ayad et al., 2006). Moreover, connexins can form both homomeric and heteromeric connexin channels. Two homomeric channels may have different permeability properties that differ from those of the heteromeric channels including both proteins (see 1.A.24.1.3; Ayad et al., 2006). Connexin23 has only 4 conserved cysteines in the extracellular domain, but they still form hemichannels (Iovine et al., 2008)  A robust and updated classification of the human 4 TMS protein complement has appeared (Attwood et al. 2016). The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional levels, and they undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function (Aasen et al. 2018).

Deletion or mutation of the various connexin isoforms produces distinctive phenotypes and pathologies. This observation reflects (1) the different molecular specificities, (2) the different relative magnitudes of transport rates of various compounds via these channels, and (3) the regulatory properties via these dissimilar channels.  Genetic diseases indicate that the normal function of CNS myelin depends on connexin32 (Cx32) and Cx47, gap junction (GJ) proteins expressed by oligodendrocytes. GJs couple oligodendrocytes to themselves (O/O channels), astrocytes to themselves (A/A channels), and oligodendrocytes to astrocytes (O/A channels). Astrocytes and oligodendrocytes express different connexins. Cx47/Cx43 and Cx32/Cx30 efficiently form functional channels, but neither Cx47 nor Cx43 formed channels with Cx30 or Cx32 (Orthoann-Murphy et al., 2007). Cx47/Cx43 and Cx32/Cx30 channels have distinct properties and permeabilities. Cx47 mutants that cause Pelizaeus-Merzbacher-like disease do not efficiently form functional channels with Cx43, indicating that disrupted Cx47/Cx43 channels cause this disease.  The mutations in connexins that give rise to disease have been summarized and discussed (Pfenniger et al. 2011).  While mutations in Cx43 are mostly linked to oculodentodigital dysplasia, Cx47 mutations are associated with Pelizaeus-Merzbacher-like disease and lymphedema. Cx40 mutations are principally linked to atrial fibrillation. Mutations in Cx37 have not yet been described, but polymorphisms in the Cx37 gene have been implicated in the development of arterial disease (Molica et al. 2014).

Maeda et al. (2009) have reported the crystal structure of the gap junction channel formed by human connexin 26 (Cx26, also known as GJB2) at 3.5 Å resolution. The density map showed the two membrane-spanning hemichannels and the arrangement of the four transmembrane helices of the six protomers forming each hemichannel. The hemichannels feature a postively charged cytoplasmic entrance, a funnel, a negatively charged transmembrane pathway, and an extracellular cavity. The pore is narrowed at the funnel, which is formed by the six amino-terminal helices lining the wall of the channel, which thus determines the molecular size restriction at the channel entrance. The structure of the Cx26 gap junction channel also has implications for the gating of the channel by the transjunctional voltage (Nakagawa et al., 2010). The N-terminal half of connexin 46 appears to contain the core elements of the pore and voltage gates (Kronengold et al., 2012). 

Research has revealed a multilevel platform via which connexins (Cxs) and pannexins (Panxs) can influence the following cellular functions within a tissue: (1) Cx gap junctional channels (GJCs) enable direct cell-cell communication of small molecules, (2) Cx hemichannels and Panx channels can contribute to autocrine/paracrine signaling pathways, and (3) different structural domains of these proteins allow for channel-independent functions, such as cell-cell adhesion, interactions with the cytoskeleton, and the activation of intracellular signaling pathways. Decrock et al. 2015 discuss their multifaceted contributions to brain development and specific processes in the NGVU, including synaptic transmission and plasticity, glial signaling, vasomotor control, and blood-brain barrier integrity in the mature CNS. Connectosomes, cell-derived lipid vesicles that contain functional gap junction channels and encapsulate molecular cargos, have been used to deliver cargos such as drugs into the cytoplasm of a cell (Gadok et al. 2016).

Connexins (Cx) contain both highly ordered domains (i.e., 4 transmembrane domains) and primarily unstructured regions (i.e., N- and C-terminal domains). The C-terminal domains vary in length and amino acid composition from the shortest on Cx26 to the longest on Cx43. With the exception of Cx26, the C-terminal domains contain multiple sites for posttranslational modification (PTM) including serines (S), threonines (T), and tyrosines (Y) for phosphorylation as well as cysteines (C) for S-nitrosylation. These PTMs are critical for regulating cellular localization, protein-protein interactions, and channel functionality (Lohman et al. 2016).

Fatty acids (FAs) have effects on connexin- and pannexin-based channels. FAs regulate diverse cellular functions, including the activities of connexin (Cx) and Panx channels which form hexameric hemichannels (HCs), which assemble into dodecameric gap junction channels (GJCs).  It has been shown that FAs decrease GJC-mediated cell-cell communication. Changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (Puebla et al. 2017). 

Connexins participate in the generation of intercellular calcium waves, in which calcium-mediated signaling responses spread to contiguous cells through gap junction to transmit calcium signaling throughout the airway epithelium. Pannexins in the nasal mucosa contribute not only to ciliary beat modulation via ATP release, but also regulation of mucus blanket components via H2O efflux. The synchronized roles of pannexin and connexin may allow effective mucociliary clearance in nasal mucosa (Ohbuchi and Suzuki 2018).

Gadok et al. 2016 have developed 'connectosomes', cell-derived lipid vesicles that contain functional gap junction channels and encapsulate molecular cargos. They showed that these vesicles form gap junctions with cells, opening a direct and efficient route for the delivery of molecular cargo to the cellular cytoplasm. Specifically, they demonstrated that using gap junctions to deliver doxorubicin reduces the therapeutically effective dose of the drug by more than an order of magnitude (Gadok et al. 2016).  Single-domain antibodies on connectosomes allows gap junction-mediated drug targetting to specific cell types (Gadok et al. 2018).

The transport reaction catalyzed by connexin gap junctions is:

Small molecules (cell 1 cytoplasm)  Small molecules (cell 2 cytoplasm)

Small molecules include small proteins, cyclic nucleotides, chemotherapeutics and small RNAs.

References associated with 1.A.24 family:

Aasen, T., S. Johnstone, L. Vidal-Brime, K.S. Lynn, and M. Koval. (2018). Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease. Int J Mol Sci 19:. 29701678
Alstrom JS., Hansen DB., Nielsen MS. and MacAulay N. (2015). Isoform-specific phosphorylation-dependent regulation of connexin hemichannels. J Neurophysiol. 114(5):3014-22. 26400258
Attwood, M.M., A. Krishnan, V. Pivotti, S. Yazdi, M.S. Almén, and H.B. Schiöth. (2016). Topology based identification and comprehensive classification of four-transmembrane helix containing proteins (4TMs) in the human genome. BMC Genomics 17: 268. 27030248
Ayad, W.A., D. Locke, I.V. Koreen, and A.L. Harris. (2006). Heteromeric, but not homomeric, connexin channels are selectively permeable to inositol phosphates. J. Biol. Chem. 281: 16727-16739. 16601118
Banerjee, D., S. Das, S.A. Molina, D. Madgwick, M.R. Katz, S. Jena, L.K. Bossmann, D. Pal, and D.J. Takemoto. (2011). Investigation of the reciprocal relationship between the expression of two gap junction connexin proteins, connexin46 and connexin43. J. Biol. Chem. 286: 24519-24533. 21606502
Bargiotas, P., H. Monyer, and M. Schwaninger. (2009). Hemichannels in cerebral ischemia. Curr Mol Med 9: 186-194. 19275626
Bevans, C.G., M. Kordel, S.K. Rhee, and A.L. Harris. (1998). Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules. J. Biol. Chem. 273: 2808-2816. 9446589
Beyer, E.C. and V.M. Berthoud. (2017). Gap junction structure: unraveled, but not fully revealed. F1000Res 6: 568. 28529713
Beyer, E.C., D.L. Paul, and D.A. Goodenough. (1987). Connexin43: a protein from rat heart homologous to a gap junction protein from liver. J. Cell Biol. 105: 2621-2629. 2826492
Bosco, D., J.A. Haefliger, and P. Meda. (2011). Connexins: key mediators of endocrine function. Physiol. Rev. 91: 1393-1445. 22013215
Brennan MJ., Karcz J., Vaughn NR., Woolwine-Cunningham Y., DePriest AD., Escalona Y., Perez-Acle T. and Skerrett IM. (2015). Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32. J Biol Chem. 290(28):17074-84. 25969535
Cascella, R., C. Strafella, S. Gambardella, G. Longo, P. Borgiani, F. Sangiuolo, G. Novelli, and E. Giardina. (2016). Two molecular assays for the rapid and inexpensive detection of GJB2 and GJB6 mutations. Electrophoresis 37: 860-864. 26681637
Coelho, J.P.L., M. Stahl, N. Bloemeke, K. Meighen-Berger, C.P. Alvira, Z.R. Zhang, S.A. Sieber, and M.J. Feige. (2019). A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration. Nat Commun 10: 672. 30737405
Da, Y., W. Wang, Z. Liu, H. Chen, L. Di, L. Previch, and Z. Chen. (2016). Aberrant trafficking of a Leu89Pro connexin32 mutant associated with X-linked dominant Charcot-Marie-Tooth disease. Neurol Res 38: 897-902. 27367520
Decrock, E., M. De Bock, N. Wang, G. Bultynck, C. Giaume, C.C. Naus, C.R. Green, and L. Leybaert. (2015). Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology? Cell Mol Life Sci 72: 2823-2851. 26118660
Derosa, A.M., C.H. Xia, X. Gong, and T.W. White. (2007). The cataract-inducing S50P mutation in Cx50 dominantly alters the channel gating of wild-type lens connexins. J. Cell. Sci. 120:4107-4116. 18003700
Ek Vitorín, J.F., T.K. Pontifex, and J.M. Burt. (2016). Determinants of Cx43 Channel Gating and Permeation: The Amino Terminus. Biophys. J. 110: 127-140. 26745416
Gabriel, L.A., R. Sachdeva, A. Marcotty, E.J. Rockwood, and E.I. Traboulsi. (2011). Oculodentodigital dysplasia: new ocular findings and a novel connexin 43 mutation. Arch Ophthalmol 129: 781-784. 21670345
Gadok, A.K., C. Zhao, A.I. Meriwether, S. Ferrati, T.G. Rowley, J. Zoldan, H.D.C. Smyth, and J.C. Stachowiak. (2018). The Display of Single-Domain Antibodies on the Surfaces of Connectosomes Enables Gap Junction-Mediated Drug Delivery to Specific Cell Populations. Biochemistry 57: 81-90. 28829120
Gadok, A.K., D.J. Busch, S. Ferrati, B. Li, H.D. Smyth, and J.C. Stachowiak. (2016). Connectosomes for Direct Molecular Delivery to the Cellular Cytoplasm. J. Am. Chem. Soc. 138: 12833-12840. 27607109
Giepmans, B.N. (2006). Role of connexin43-interacting proteins at gap junctions. Adv Cardiol 42: 41-56. 16646583
Goldberg, G.S., A.P. Moreno, and P.D. Lampe. (2002). Gap junctions between cells expressing connexon 43 or 32 show inverse permselectivity to adenosine and ATP. J. Biol. Chem. 277: 36725-36730. 12119284
Grek, C.L., J.M. Rhett, J.S. Bruce, G.S. Ghatnekar, and E.S. Yeh. (2016). Connexin 43, breast cancer tumor suppressor: Missed connections? Cancer Lett 374: 117-126. 26884256
Hervé, J.C., M. Derangeon, D. Sarrouilhe, B.N. Giepmans, and N. Bourmeyster. (2012). Gap junctional channels are parts of multiprotein complexes. Biochim. Biophys. Acta. 1818: 1844-1865. 22197781
Hervé, J.C., P. Phelan, R. Bruzzone, and T.W. White. (2005). Connexins, innexins and pannexins: bridging the communication gap. Biochim. Biophys. Acta. 1719: 3-5. 16359939
Hong, H.M., J.J. Yang, C.C. Su, J.Y. Chang, T.C. Li, and S.Y. Li. (2010). A novel mutation in the connexin 29 gene may contribute to nonsyndromic hearing loss. Hum Genet 127: 191-199. 19876648
Hua, V.B., A.B. Chang, J.H. Tchieu, P.A. Nielsen, and M.H. Saier, Jr. (2003). Sequence and phylogenetic analysis of 4 TMS junctional proteins: Connexins, innexins, claudins and occludins. J. Mem. Biol. 194: 59-76. 14502443
Iossa, S., E. Marciano, and A. Franzé. (2011). GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss. Curr Genomics 12: 475-785. 22547955
Iovine, M.K., A.M. Gumpert, M.M. Falk, and T.C. Mendelson. (2008). Cx23, a connexin with only four extracellular-loop cysteines, forms functional gap junction channels and hemichannels. FEBS Lett. 582: 165-170. 18068130
Jara O., Acuna R., Garcia IE., Maripillan J., Figueroa V., Saez JC., Araya-Secchi R., Lagos CF., Perez-Acle T., Berthoud VM., Beyer EC. and Martinez AD. (2012). Critical role of the first transmembrane domain of Cx26 in regulating oligomerization and function. Mol Biol Cell. 23(17):3299-311. 22787277
Kang, J., N. Kang, D. Lovatt, A. Torres, Z. Zhao, J. Lin, and M. Nedergaard. (2008). Connexin 43 hemichannels are permeable to ATP. J. Neurosci. 28: 4702-4711. 18448647
Kar, R., N. Batra, M.A. Riquelme, and J.X. Jiang. (2012). Biological role of connexin intercellular channels and hemichannels. Arch Biochem Biophys 524: 2-15. 22430362
Katoch, P., S. Mitra, A. Ray, L. Kelsey, B.J. Roberts, J.K. Wahl, 3rd, K.R. Johnson, and P.P. Mehta. (2015). The carboxyl tail of connexin32 regulates gap junction assembly in human prostate and pancreatic cancer cells. J. Biol. Chem. 290: 4647-4662. 25548281
Kim, D.Y., Y. Kam, S.K. Koo, and C.O. Joe. (1998). Gating connexin 43 channels reconstituted in lipid vesicles by mitogen-activated protein kinase phosphorylation. J. Biol. Chem. 274: 5581-5587. 10026174
Kim, I.S., P. Ganesan, and D.K. Choi. (2016). Cx43 Mediates Resistance against MPP⁺-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells via Modulating the Mitochondrial Apoptosis Pathway. Int J Mol Sci 17:. 27809287
Kopanic, J.L., B. Schlingmann, M. Koval, A.F. Lau, P.L. Sorgen, and V.F. Su. (2015). Degradation of gap junction connexins is regulated by the interaction with Cx43-interacting protein of 75 kDa (CIP75). Biochem. J. 466: 571-585. 25583071
Kovacs, J.A., K.A. Baker, G.A. Altenberg, R. Abagyan, and M. Yeager. (2007). Molecular modeling and mutagenesis of gap junction channels. Prog Biophys Mol Biol 94: 15-28. 17524457
Kronengold, J., M. Srinivas, and V.K. Verselis. (2012). The N-terminal half of the connexin protein contains the core elements of the pore and voltage gates. J. Membr. Biol. 245: 453-463. 22825713
Kuo, D.S., J.T. Sokol, P.J. Minogue, V.M. Berthoud, A.M. Slavotinek, E.C. Beyer, and D.B. Gould. (2017). Characterization of a variant of gap junction protein α8 identified in a family with hereditary cataract. PLoS One 12: e0183438. 28827829
Kyle JW., Berthoud VM., Kurutz J., Minogue PJ., Greenspan M., Hanck DA. and Beyer EC. (2009). The N terminus of connexin37 contains an alpha-helix that is required for channel function. J Biol Chem. 284(30):20418-27. 19478091
Leithe, E. and E. Rivedal. (2007). Ubiquitination of gap junction proteins. J. Membr. Biol. 217: 43-51. 17657522
Liang, W.G., C.C. Su, J.H. Nian, A.S. Chiang, S.Y. Li, and J.J. Yang. (2011). Human connexin30.2/31.3 (GJC3) does not form functional gap junction channels but causes enhanced ATP release in HeLa cells. Cell Biochem Biophys 61: 189-197. 21480002
Liu, F., F.T. Arce, S. Ramachandran, and R. Lal. (2006). Nanmechanics of hemichannel conformations. Connexin flexibility underlying channel opening and closing. J. Biol. Chem. 281: 23207-23217. 16769719
Lohman, A.W., A.C. Straub, and S.R. Johnstone. (2016). Identification of Connexin43 Phosphorylation and S-Nitrosylation in Cultured Primary Vascular Cells. Methods Mol Biol 1437: 97-111. 27207289
Lukashkina, V.A., S. Levic, A.N. Lukashkin, N. Strenzke, and I.J. Russell. (2017). A connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics. Nat Commun 8: 14530. 28220769
Maeda, S., S. Nakagawa, M. Suga, E. Yamashita, A. Oshima, Y. Fujiyoshi, and T. Tsukihara. (2009). Structure of the connexin 26 gap junction channel at 3.5 Å resolution. Nature 458: 597-602. 19340074
Meens MJ., Pfenniger A., Kwak BR. and Delmar M. (2013). Regulation of cardiovascular connexins by mechanical forces and junctions. Cardiovasc Res. 99(2):304-14. 23612582
Misu, A., H. Yamanaka, T. Aramaki, S. Kondo, I.M. Skerrett, M.K. Iovine, and M. Watanabe. (2016). Two Different Functions of Connexin43 Confer Two Different Bone Phenotypes in Zebrafish. J. Biol. Chem. 291: 12601-12611. 27129238
Molica, F., M.J. Meens, S. Morel, and B.R. Kwak. (2014). Mutations in cardiovascular connexin genes. Biol Cell 106: 269-293. 24966059
Nakagawa, S., S. Maeda, and T. Tsukihara. (2010). Structural and functional studies of gap junction channels. Curr. Opin. Struct. Biol. 20: 423-430. 20542681
Ohbuchi, T. and H. Suzuki. (2018). Synchronized roles of pannexin and connexin in nasal mucosal epithelia. Eur Arch Otorhinolaryngol. [Epub: Ahead of Print] 29574598
Orthmann-Murphy, J.L., M. Freidin, E. Fischer, S.S. Scherer, and C.K. Abrams. (2007). Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. J. Neurosci. 27: 13949-13957. 18094232
Pfenniger, A., A. Wohlwend, and B.R. Kwak. (2011). Mutations in connexin genes and disease. Eur J Clin Invest 41: 103-116. 20840374
Pinto, B.I., I.E. García, A. Pupo, M.A. Retamal, A.D. Martínez, R. Latorre, and C. González. (2016). Charged residues at the first transmembrane region contribute to the voltage dependence of connexins slow gate. J. Biol. Chem. [Epub: Ahead of Print] 27143357
Press, E.R., Q. Shao, J.J. Kelly, K. Chin, A. Alaga, and D.W. Laird. (2017). Induction of cell death and gain-of-function properties of connexin26 mutants predict severity of skin disorders and hearing loss. J. Biol. Chem. [Epub: Ahead of Print] 28428247
Puebla, C., B.A. Cisterna, D.P. Salas, F. Delgado-López, P.D. Lampe, and J.C. Sáez. (2016). Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism. Biochim. Biophys. Acta. 1861: 439-448. 26869446
Puebla, C., M.A. Retamal, R. Acuña, and J.C. Sáez. (2017). Regulation of Connexin-Based Channels by Fatty Acids. Front Physiol 8: 11. 28174541
Puk, O., J. Löster, C. Dalke, D. Soewarto, H. Fuchs, B. Budde, P. Nürnberg, E. Wolf, M.H. de Angelis, and J. Graw. (2008). Mutation in a novel connexin-like gene (Gjf1) in the mouse affects early lens development and causes a variable small-eye phenotype. Invest Ophthalmol Vis Sci 49: 1525-1532. 18385072
Rash, J.E., K.G. Vanderpool, T. Yasumura, J. Hickman, J.T. Beatty, and J.I. Nagy. (2016). KV1 channels identified in rodent myelinated axons, linked to Cx29 in innermost myelin: support for electrically active myelin in mammalian saltatory conduction. J Neurophysiol 115: 1836-1859. 26763782
Ribeiro-Rodrigues, T.M., T. Martins-Marques, S. Morel, B.R. Kwak, and H. Girão. (2017). Role of connexin 43 in different forms of intercellular communication - gap junctions, extracellular vesicles and tunnelling nanotubes. J Cell Sci 130: 3619-3630. 29025971
Sanchez, H.A., N. Slavi, M. Srinivas, and V.K. Verselis. (2016). Syndromic deafness mutations at Asn 14 differentially alter the open stability of Cx26 hemichannels. J Gen Physiol 148: 25-42. 27353444
Šeda, O., D. Křenová, O. Oliyarnyk, L. Šedová, M. Krupková, F. Liška, B. Chylíková, L. Kazdová, and V. Křen. (2016). Heterozygous connexin 50 mutation affects metabolic syndrome attributes in spontaneously hypertensive rat. Lipids Health Dis 15: 199. 27871290
Shin, D.J., A.L. Germann, A.D. Johnson, S.A. Forman, J.H. Steinbach, and G. Akk. (2018). Propofol Is an Allosteric Agonist with Multiple Binding Sites on Concatemeric Ternary GABA Receptors. Mol Pharmacol 93: 178-189. 29192122
Slavi, N., A.H. Toychiev, S. Kosmidis, J. Ackert, S.A. Bloomfield, H. Wulff, S. Viswanathan, P.D. Lampe, and M. Srinivas. (2018). Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy. Proc. Natl. Acad. Sci. USA 115: E5934-E5943. 29891713
Stridh, M.H., M. Tranberg, S.G. Weber, F. Blomstrand, and M. Sandberg. (2008). Stimulated efflux of amino acids and glutathione from cultured hippocampal slices by omission of extracellular calcium: likely involvement of connexin hemichannels. J. Biol. Chem. 283(16): 10347-10356. 18272524
Su, C.C., S.Y. Li, Y.C. Yen, J.H. Nian, W.G. Liang, and J.J. Yang. (2013). Mechanism of two novel human GJC3 missense mutations in causing non-syndromic hearing loss. Cell Biochem Biophys 66: 277-286. 23179405
Sugiura, K., M. Arima, K. Matsunaga, and M. Akiyama. (2015). The novel GJB3 mutation p.Thr202Asn in the M4 transmembrane domain underlies erythrokeratodermia variabilis. Br J Dermatol 173: 309-311. 25556823
Tarzemany, R., G. Jiang, H. Larjava, and L. Häkkinen. (2015). Expression and function of connexin 43 in human gingival wound healing and fibroblasts. PLoS One 10: e0115524. 25584940
Teubner B., B. Odermatt, M. Guldenagel, G. Sohl, J. Degen, F. Bukauskas, J. Kronengold, V.K. Verselis, Y.T. Jung, C.A. Kozak, K. Schilling, K. Willecke. (2001). Functional expression of the new gap junction gene connexin47 transcribed in mouse brain and spinal cord neurons. J. Neurosci. 21: 1117-1126. 11160382
Unger, V.M., N.M. Kumar, N.B. Gilula, and M. Yeager. (1999). Three-dimensional structure of a recombinant gap junction membrane channel. Science 283: 1176-1180. 10024245
Valdez Capuccino, J.M., P. Chatterjee, I.E. García, W.M. Botello-Smith, H. Zhang, A.L. Harris, Y. Luo, and J.E. Contreras. (2018). The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening. J Gen Physiol. [Epub: Ahead of Print] 30530766
Valiunas V., R. Mui, E. McLachlan, G. Valdimarsson, P.R. Brink, T.W. White. (2004). Biophysical characterization of zebrafish connexin35 hemichannels. Am J Physiol. Cell Physiol. 287: C1596-1604 15282192
Verselis, V.K. (2017). Connexin hemichannels and cochlear function. Neurosci Lett. [Epub: Ahead of Print] 28917982
Wang, C.H., A.W. Duster, B.O. Aydintug, M.G. Zarecki, and H. Lin. (2018). Chloride Ion Transport by theCLC Cl/HAntiporter: A Combined Quantum-Mechanical and Molecular-Mechanical Study. Front Chem 6: 62. 29594103
Wang, J., Z.Y. Yang, Y.F. Guo, J.Y. Kuang, X.W. Bian, and S.C. Yu. (2017). Targeting different domains of gap junction protein to control malignant glioma. Neuro Oncol. [Epub: Ahead of Print] 29106645
Wang, K.J. and S.Q. Zhu. (2012). A novel p.F206I mutation in Cx46 associated with autosomal dominant congenital cataract. Mol Vis 18: 968-973. 22550389
White, T.W. and D.L. Paul. (1999). Genetic diseases and gene knockouts reveal diverse connexin functions. Annu. Rev. Physiol. 61: 283-310. 10099690
White, T.W., H. Wang, R. Mui, J. Litteral, and P.R. Brink. (2004). Cloning and functional expression of invertebrate connexins from Halocynthia pyriformis. FEBS Lett. 577: 42-48. 15527759
Wong, S.H., W.H. Wang, P.H. Chen, S.Y. Li, and J.J. Yang. (2017). Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene. Int J Med Sci 14: 246-256. 28367085
Yeager, M. and N.B. Gilula. (1992). Membrane topology and quaternary structure of cardiac gap junction ion channels. J. Mol. Biol. 223: 929-948. 1371548
Yeager, M., V.M. Unger, and M.M. Falk. (1998). Synthesis, assembly and structure of gap junction intercellular channels. Curr. Opin. Struct. Biol. 8: 517-524. 9729745
Zhang, D., C. Zhou, Q. Wang, L. Cai, W. Du, X. Li, X. Zhou, and J. Xie. (2018). Extracellular Matrix Elasticity Regulates Osteocyte Gap Junction Elongation: Involvement of Paxillin in Intracellular Signal Transduction. Cell Physiol Biochem 51: 1013-1026. 30476913
Zhang, X., T. Zou, Y. Liu, and Y. Qi. (2006). The gating effect of calmodulin and calcium on the connexin50 hemichannel. Biol Chem 387: 595-601. 16740131
Zhang, X.H., J. Da Wang, H.Y. Jia, J.S. Zhang, Y. Li, Y. Xiong, J. Li, X.X. Li, Y. Huang, G.Y. Zhu, S.S. Rong, M. Wormstone, and X.H. Wan. (2018). Mutation profiles of congenital cataract genes in 21 northern Chinese families. Mol Vis 24: 471-477. 30078984
Zhou JZ. and Jiang JX. (2014). Gap junction and hemichannel-independent actions of connexins on cell and tissue functions--an update. FEBS Lett. 588(8):1186-92. 24434539
Zonta, F., D. Buratto, G. Crispino, A. Carrer, F. Bruno, G. Yang, F. Mammano, and S. Pantano. (2018). Cues to Opening Mechanisms From Electric Field Excitation of Cx26 Hemichannel and Mutagenesis Studies in HeLa Transfectans. Front Mol Neurosci 11: 170. 29904340