Skip to main content

Gap Junction Morphology and Dynamics in Situ

  • Chapter
Connexins

Abstract

Gap junctions serve important functions in direct intercellular communication in almost all vertebrate cell types. Cells dynamically modulate gap junctional communication by regulating the synthesis, transport, gating, and turnover of the constituent junctional channels. Since the discovery of gap junctions by electron microscopic techniques, much insight has been gained about their molecular composition and regulation. The term gap junction refers not only to the dodecameric connexin channels, but also to the two plasma membranes that they span. The plaques formed by clustered connexin channels have various packing arrangements that may be related to functionality or interaction with cytosolic binding partner proteins. The lipid composition within plaques contains a relatively high percentage of cholesterol, which confers rigidity on the structure and decreased lateral mobility to the intercellular channels. This is not the case for connexin hemichannels in nonjunctional membranes, which actively traffic laterally within the plasma membrane to plaques in cell–cell apposition areas. Moreover, connexin-interacting proteins may contribute to regulation of how connexin channels pack in gap junctions. These partners are part of the “nexus”, that is, a specialized and integrated area of the cell membrane involved in intercellular communication.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Goodenough DA, Revel J-P. A fine structural analysis of intercellular gap junctions in the mouse liver. J Cell Biol. 1970;45:272–90.

    Article  CAS  PubMed  Google Scholar 

  2. Gilula NB, Reeves OR, Steinbach A. Metabolic coupling, ionic coupling, and cell contacts. Nature. 1972;235:262–5.

    Article  CAS  PubMed  Google Scholar 

  3. Goodenough DA. Bulk isolation of mouse hepatocyte gap junctions. Characterization of the principle protein, connexin. J Cell Biol. 1974;61:557–63.

    Article  CAS  PubMed  Google Scholar 

  4. Braun J, Abney JR, Owicki JC. How a gap junction maintains its structure. Nature. 1984;310:316–8.

    Article  CAS  PubMed  Google Scholar 

  5. Severs NJ, Shotton DM, editors. Rapid freezing, freeze-fracture, and deep etching. New York: Wiley-Liss; 1995.

    Google Scholar 

  6. Hirokawa N, Heuser J. The inside and outside of gap junction membranes visualized by deep etching. Cell. 1982;30:395–406.

    Article  CAS  PubMed  Google Scholar 

  7. Fujimoto K, Nagafuchi A, Tsukita S, Kuraoka A, Ohokuma A, Shibata Y. Dynamics of connexins, E-cadherin and α-catenin on cell membranes duing gap junction formation. J Cell Sci. 1997;110:311–322.

    Google Scholar 

  8. Giepmans BN, Adams SR, Ellisman MH, Tsien RY. The fluorescent toolbox for assessing protein location and function. Science. 2006;312:217–24.

    Article  CAS  PubMed  Google Scholar 

  9. Shivers RR, McVicar LK. Gap junctions revealed by freeze-fracture electron microscopy. Microsc Res Tech. 1995;31:437–45.

    Article  CAS  PubMed  Google Scholar 

  10. Sosinsky GE, Baker TS, Caspar DLD, Goodenough DA. Correlation analysis of gap junction lattices. Biophys J. 1990;58:1213–26.

    Article  CAS  PubMed  Google Scholar 

  11. Skepper JN, Navarantnam V. Variations in the structure of nexuses in the myocardium of the golden hamster Mesocrietus auratus. J Anat. 1986;149:143–55.

    CAS  PubMed  Google Scholar 

  12. Windoffer R, Beile B, Leibold A, Thomas S, Wilhelm U, Leube RE. Visualization of gap junction mobility in living cells. Cell Tissue Res. 2000;299:347–62.

    Article  CAS  PubMed  Google Scholar 

  13. Kuraoka A, Iida H, Hatae T, Shibata Y, Itoh M, Kurita T. Location of gap junction proteins, connexins 32 and 26, in rat and guinea pig liver as revealed by quick-freeze, deep-etch immunoelectron microscopy. J Histochem Cytochem. 1993;41:971–80.

    CAS  PubMed  Google Scholar 

  14. Rash JE, Dillman RK, Morita M, Whalen LR, Guthrie PB, Fay-Guthrie D, Wheeler DW. Grid-mapped freeze-fracture: correlative confocal laser scanning microscopy and freeze-fracture electron microscopy of preselected cells in tissue slices. In: Severs NJ, Shotton DM, editors. Rapid Freezing, Freeze-fracture and Deep Etching. New York, Wiley-Liss, 1995.

    Google Scholar 

  15. Zampighi GA, Planells AM, Lin D, Takemoto D. Regulation of lens cell-to-cell communication by activation of PKCγ and disassembly of Cx50 channels. Invest Ophthalmol Vis Sci. 2005;46:3247–55.

    Article  PubMed  Google Scholar 

  16. Biswas SK, Lo WK. Gap junctions contain different amounts of cholesterol which undergo unique sequestering processes during fiber cell differentiation in the embryonic chicken lens. Mol Vis. 2007;13:345–59.

    CAS  PubMed  Google Scholar 

  17. Kamasawa N, Furman CS, Davidson KG, Rash JE, Sampson JA, Magnie AR, Gebhardt BR, Kamasawa M, Yasumura T, Zumbrunnen JR, Pickard GE, Nagy JI. Abundance and ultrastructural diversity of neuronal gap junctions in the OFF and ON sublaminae of the inner plexiform layer of rat and mouse retina. Neuroscience. 2006;142:1093–117.

    Article  CAS  PubMed  Google Scholar 

  18. Raviola E, Goodenough DA, Raviola G. Structure of rapidly frozen gap junctions. J Cell Biol. 1980;87:273–9.

    Article  CAS  PubMed  Google Scholar 

  19. Peracchia C, Peracchia LL. Gap junction dynamics: reversible effect of hydrogen ions. J Cell Biol. 1980;87:719–27.

    Article  CAS  PubMed  Google Scholar 

  20. Peracchia C, Peracchia LL. Gap junction dynamics: reversible effects of divalent cations. J Cell Biol. 1980;87:708–18.

    Article  CAS  PubMed  Google Scholar 

  21. Page E, Karrison T, Upshaw-Earley J. Freeze-fractured cardiac gap junctions: structural analysis by three methods. Am J Physiol. 1983;244:H525–39.

    CAS  PubMed  Google Scholar 

  22. Peracchia C. Calcium effects on gap junction structure and cell coupling. Nature. 1978;271:669–71.

    Article  CAS  PubMed  Google Scholar 

  23. Buzhynskyy N, Hite RK, Walz T, Scheuring S. The supramolecular architecture of junctional microdomains in native lens membranes. EMBO Rep. 2007;8:51–5.

    Article  CAS  PubMed  Google Scholar 

  24. Scheuring S, Buzhynskyy N, Jaroslawski S, Goncalves RP, Hite RK, Walz T. Structural models of the supramolecular organization of AQP0 and connexons in junctional microdomains. J Struct Biol. 2007;160:385–94.

    Article  CAS  PubMed  Google Scholar 

  25. Rash JE, Yasumura T, Dudek FE, Nagy JI. Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. J Neurosci. 2001;21:1983–2000.

    CAS  PubMed  Google Scholar 

  26. Rash J, Pickard G, Davidson K, O’Brien J, Hartwick A, Kamasawa N, Yasumura T, Nagy J. Exposure to dopamine and its D1 receptor antagonist SCH23390 produces large-scale ultrastructural plasticity and changes in phosphorylation of connexin36 in neuronal gap junctions of adult rat retina. ASCB Annual Meeting. 2007;910.

    Google Scholar 

  27. Harris AL. Emerging issues of connexin channels: biophysics fills the gap. Q Rev Biophys. 2001;34:325–472.

    CAS  Google Scholar 

  28. Cottrell GT, Burt JM. Functional consequences of heterogeneous gap junction channel formation and its influence in health and disease. Biochim Biophys Acta. 2005;1711:126–41.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang J-T, Nicholson BJ. The topological structure of connexin 26 and its distribution compared to connexin 32 in hepatic gap junctions. J Membr Biol. 1994;139:15–29.

    CAS  PubMed  Google Scholar 

  30. Risek B, Klier FG, Gilula NB. Developmental regulation and structural organization of connexins in epidermal gap junctions. Dev Biol. 1994;164:183–96.

    Article  CAS  PubMed  Google Scholar 

  31. Laird DW, Jordan K, Thomas T, Qin H, Fistouris P, Shao Q. Comparative analysis and application of fluorescent protein-tagged connexins. Microsc Res Tech. 2001;52:263–72.

    Article  CAS  PubMed  Google Scholar 

  32. Falk M. Connexin-specific distribution within gap junctions revealed in living cells. J Cell Sci. 2000;113:4109–20.

    CAS  PubMed  Google Scholar 

  33. Falk MM, Lauf U. High-affinity, fluorescence deconvolution microscopy and tagging with the autofluorescent tracers CFP, GFP, and YFP to study the structural composition of gap junctions in living cells. Microsc Res Tech. 2001;52:251–62.

    Article  CAS  PubMed  Google Scholar 

  34. Gu Y, Di WL, Kelsell DP, Zicha D. Quantitative fluorescence resonance energy transfer (FRET) measurement with acceptor photobleaching and spectral unmixing. J Microsc. 2004;215:162–73.

    Article  CAS  PubMed  Google Scholar 

  35. Di WL, Gu Y, Common JE, Aasen T, O Toole EA, Kelsell DP, Zicha D. Connexin interaction patterns in keratinocytes revealed morphologically and by FRET analysis. J Cell Sci. 2005;118:1505–14

    Article  CAS  PubMed  Google Scholar 

  36. Sosinsky GE. Mixing of connexins in gap junction membrane channels. Proc Natl Acad Sci USA. 1995;92:9210–14.

    Article  CAS  PubMed  Google Scholar 

  37. Harris AL, Walter A, Paul D, Goodenough DA, Zimmerberg J. Ion channels in single bilayers induced by rat connexin32. Molec Brain Res. 1992;15:269–80.

    Article  CAS  PubMed  Google Scholar 

  38. Jiang JX, Goodenough DA. Heteromeric connexons in lens gap junction channels. Proc Natl Acad Sci USA. 1996;3:1287–91.

    Article  Google Scholar 

  39. Cascio M. Connexins and their environment: effects of lipids composition on ion channels. Biochim Biophys Acta. 2005;1711:142–53.

    Article  CAS  PubMed  Google Scholar 

  40. Makowski L, Caspar DLD, Phillips WC, Goodenough DA. Gap junction structure II. Analysis of the X-ray diffraction data. J Cell Biol. 1977;74:629–45.

    Article  CAS  PubMed  Google Scholar 

  41. Badger J, Caspar DL. Water structure in cubic insulin crystals. Proc Natl Acad Sci USA. 1991;88:622–6.

    Article  CAS  PubMed  Google Scholar 

  42. Valiyaveetil FI, Zhou Y, MacKinnon R. Lipids in the structure, folding, and function of the KcsA K+ channel. Biochem. 2002;41:10771–7.

    Article  CAS  Google Scholar 

  43. Evans WH, Gurd JW. Preparation and properties of nexus and lipid enriched vesicles from mouse liver plasma membranes. Biochem J. 1972;128:691–700.

    CAS  PubMed  Google Scholar 

  44. Hertzberg EL. A detergent independent procedure for the isolation of gap junctions from rat liver. J Biol Chem. 1984;259:9936–43.

    CAS  PubMed  Google Scholar 

  45. Hand GM, Müller DJ, Nicholson BJ, Engel A, Sosinsky GE. Isolation and characterization of gap junctions from tissue culture cells. J Mol Biol. 2002;315:587–600.

    Article  CAS  PubMed  Google Scholar 

  46. Gogol E, Unwin N. Organization of connexons in isolated rat liver gap junctions. Biophys J. 1988;54:105–12.

    Article  CAS  PubMed  Google Scholar 

  47. Makowski L, Caspar DLD, Goodenough DA, Phillips WC. Gap junction structures III. The effect of variations in isolation procedures. Biophys J. 1982;37:189–91.

    Article  CAS  PubMed  Google Scholar 

  48. Sosinsky GE, Nicholson BJ. Structural organization of gap junction channels. Biochim Biophys Acta. 2005;1711:99–125.

    Article  CAS  PubMed  Google Scholar 

  49. Malewicz B, Kumar VV, Johnson RG, Baumann WJ. Lipids in gap junction assembly and function. Lipids. 1990;25:419–27.

    Article  CAS  PubMed  Google Scholar 

  50. Ghoshroy S, Goodenough DA, Sosinsky GE. Preparation, characterization, and structure of half gap junctional layers split with urea and EGTA. J Membr Biol. 1995;146:15–28.

    CAS  PubMed  Google Scholar 

  51. Caspar DLD, Goodenough DA, Makowski L, Phillips WC. Gap junctions structures I. correlated electron microscopy and X-ray diffraction. J Cell Biol. 1977;74:605–28.

    Article  CAS  PubMed  Google Scholar 

  52. Unger VM, Kumar NM, Gilula NB, Yeager M. Three-dimensional structure of a recombinant gap junction membrane channel. Science. 1999;283:1176–80.

    Article  CAS  PubMed  Google Scholar 

  53. Oshima A, Tani K, Hiroaki Y, Fujiyoshi Y, Sosinsky GE. Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule. Proc Natl Acad Sci USA. 2007;104:10034–9.

    Article  CAS  PubMed  Google Scholar 

  54. Henderson D, Eibl H, Weber K. Structure and biochemistry of mouse hepatic gap junctions. J Mol Biol. 1979;132:193–218.

    Article  CAS  PubMed  Google Scholar 

  55. Meyer R, Malewicz B, Baumann WJ, Johnson RG. Increased gap junction assembly between cultured cells upon cholesterol supplementation. J Cell Sci. 1990;96:231–8.

    CAS  PubMed  Google Scholar 

  56. Locke D, Harris AL. Interactions of hemi- and junctional channels with different phospholipids. Biophys J. 2007;92:443a.

    Google Scholar 

  57. Rhee SK, Bevans CG, Harris AL. Channel-forming activity of immunoaffinity-purified connexin32 in single phospholipid membranes. Biochem. 1996;35:9212–23.

    Article  CAS  Google Scholar 

  58. Brown DA, London E. Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol. 1998;14:111–36.

    Article  CAS  PubMed  Google Scholar 

  59. Simons K, Ikonen E. Functional rafts in cell membranes. Nature. 1997;387:569–72.

    Article  CAS  PubMed  Google Scholar 

  60. Anderson RG, Jacobson K. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science. 2002;296:1821–5.

    Article  CAS  PubMed  Google Scholar 

  61. Parton RG, Richards AA. Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic. 2003;4:724–38.

    Article  CAS  PubMed  Google Scholar 

  62. Shogomori H, Brown DA. Use of detergents to study membrane rafts: the good, the bad, and the ugly. Biol Chem. 2003;384:1259–63.

    Article  CAS  PubMed  Google Scholar 

  63. Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG. Caveolin, a protein component of caveolae membrane coats. Cell. 1992;68:673–82.

    Article  CAS  PubMed  Google Scholar 

  64. Neufeld EB, Cooney AM, Pitha J, Dawidowicz EA, Dwyer NK, Pentchev PG, Blanchette-Mackie EJ. Intracellular trafficking of cholesterol monitored with a cyclodextrin. J Biol Chem. 1996;271:21604–13.

    Article  CAS  PubMed  Google Scholar 

  65. Orlandi PA, Fishman PH. Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. J Cell Biol. 1998;141:905–15.

    Article  CAS  PubMed  Google Scholar 

  66. Allen JA, Halverson-Tamboli RA, Rasenick MM. Lipid raft microdomains and neurotransmitter signaling. Nat Rev Neurosci. 2007;8:128–40.

    Article  CAS  PubMed  Google Scholar 

  67. Brown DA. Lipid rafts, detergent-resistant membranes, and raft targeting signals. Physiology. 2006;21:430–9.

    Article  CAS  PubMed  Google Scholar 

  68. Michel V, Bakovic M. Lipid rafts in health and disease. Biol Cell. 2007;99:129–40.

    Article  CAS  PubMed  Google Scholar 

  69. Lin D, Zhou J, Zelenka PS, Takemoto DJ. Protein kinase Cγ regulation of gap junction activity through caveolin-1-containing lipid rafts. Invest Ophthalmol Vis Sci. 2003;44:5259–68.

    Article  PubMed  Google Scholar 

  70. Hur EM, Park YS, Lee BD, Jang IH, Kim HS, Kim TD, Suh PG, Ryu SH, Kim KT. Sensitization of epidermal growth factor-induced signaling by bradykinin is mediated by c-Src. Implications for a role of lipid microdomains. J Biol Chem. 2004;279:5852–60.

    Article  CAS  PubMed  Google Scholar 

  71. Giepmans BN, Hengeveld T, Postma FR, Moolenaar WH. Interaction of c-Src with gap junction protein connexin-43. Role in the regulation of cell-cell communication. J Biol Chem. 2001;276:8544–9.

    Article  CAS  PubMed  Google Scholar 

  72. Schubert AL, Schubert W, Spray DC, Lisanti MP. Connexin family members target to lipid raft domains and interact with caveolin-1. Biochem. 2002;41:5754–64.

    Article  CAS  Google Scholar 

  73. Locke D, Liu J, Harris AL. Lipid rafts prepared by different methods contain different connexin channels, but gap junctions are not lipid rafts. Biochem. 2005;44:13027–42.

    Article  CAS  Google Scholar 

  74. Martin PE, George CH, Castro C, Kendall JM, Capel J, Campbell AK, Revilla A, Barrio LC, Evans WH. Assembly of chimeric connexin-aequorin proteins into functional gap junction channels: reporting intracellular and plasma membrane calcium environments. J Biol Chem. 1998;273:1719–26.

    Article  CAS  PubMed  Google Scholar 

  75. Jordan K, Solan JL, Dominguez M, Sia M, Hand A, Lampe PD, Laird DW. Trafficking, assembly, and function of a connexin43-green fluorescent protein chimera in live mammalian cells. Molec Biol Cell. 1999;10:2033–50.

    CAS  PubMed  Google Scholar 

  76. Gaietta G, Deerinck TJ, Adams SR, Bouwer J, Tour O, Laird DW, Sosinsky GE, Tsien RY, Ellisman MH. Multicolor and electron microscopic imaging of connexin trafficking. Science. 2002;296:503–7.

    Article  CAS  PubMed  Google Scholar 

  77. Hunter AW, Jourdan J, Gourdie RG. Fusion of GFP to the carboxyl terminus of connexin43 increases gap junction size in HeLa cells. cell Commun Adhes. 2003;10:211–14.

    CAS  PubMed  Google Scholar 

  78. Lopez P, Balicki D, Buehler LK, Falk MM, Chen SC. Distribution and dynamics of gap junction channels revealed in living cells. Cell Commun Adhes. 2001;8:237–42.

    Article  CAS  PubMed  Google Scholar 

  79. Contreras JE, Sáez JC, Bukauskas FF, Bennett MVL. Gating and regulation of connexin 43 (Cx43) hemichannels. Proc Natl Acad Sci USA. 2003;100:11388–93.

    Article  CAS  PubMed  Google Scholar 

  80. Bukauskas FF, Jordan K, Bukauskiene A, Bennett MV, Lampe PD, Laird DW, Verselis VK. Clustering of connexin43-enhanced green fluorescent protein gap junction channels and functional coupling in living cells. Proc Natl Acad Sci USA. 2000;97:2556–61.

    Article  CAS  PubMed  Google Scholar 

  81. Laird DW. The life cycle of a connexin: gap junction formation, removal, and degradation. J Bioener Biomembr. 1996;28:311–8.

    Article  CAS  Google Scholar 

  82. Musil LS, Le A-CN, VanSlyke JK, Roberts LM. Regulation of connexin degradation as a mechanism to increase gap junction assembly and function. J Biol Chem. 2000;275:25207–15.

    Article  CAS  PubMed  Google Scholar 

  83. Fallon RF, Goodenough DA. Five-hrs half-life of mouse liver gap junction protein. J Cell Biol. 1981;90:521–6.

    Article  CAS  PubMed  Google Scholar 

  84. Beardslee MA, Laing JG, Beyer EC, Saffitz JE. Rapid turnover of connexin43 in the adult rat heart. Circ Res. 1998;83:629–35.

    CAS  PubMed  Google Scholar 

  85. Musil LS, Beyer EC, Goodenough DA. Expression of the gap junction protein connexin43 in embryonic chick lens: molecular cloning, ultrastructural localization, and posttranslational phosphorylation. J Membr Biol. 1990;116:163–75.

    Article  CAS  PubMed  Google Scholar 

  86. Jiang JX, Goodenough DA. Phosphorylation of lens-fiber connexins in lens organ cultures. Eur J Biochem. 1998;255:37–44.

    Article  CAS  PubMed  Google Scholar 

  87. Berthoud VM, Bassnett S, Beyer EC. Cultured chicken embryo lens cells resemble differentiating fiber cells in vivo and contain two kinetic pools of connexin56. Exp Eye Res. 1999;68:475–84.

    Article  CAS  PubMed  Google Scholar 

  88. VanSlyke JK, Musil LS. Cytosolic stress reduces degradation of connexin43 internalized from the cell surface and enhances gap junction formation and function. Mol Biol Cell. 2005;16:5247–57.

    Article  CAS  PubMed  Google Scholar 

  89. Solan JL, Fry MD, TenBroek EM, Lampe PD. Connexin43 phosphorylation at S368 is acute during S and G2/M and in response to protein kinase C activation. J Cell Sci. 2003;116:2203–11.

    Article  CAS  PubMed  Google Scholar 

  90. Gerken M, Thews E, Tietz C, Wrachtrup J, Eckert R. Diffusion behavior of gap junction hemichannels in living cells. Curr Pharm Biotechnol. 2005;6:151–8.

    Article  CAS  PubMed  Google Scholar 

  91. Neijssen J, Herberts C, Drijfhout JW, Reits E, Janssen L, Neefjes J. Cross-presentation by intercellular peptide transfer through gap junctions. Nature. 2005;434:83–8.

    Article  CAS  PubMed  Google Scholar 

  92. Lauf U, Giepmans BN, Lopez P, Braconnot S, Chen SC, Falk MM. Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells. Proc Natl Acad Sci USA. 2002;99:10446–51.

    Article  CAS  PubMed  Google Scholar 

  93. Shaw RM, Fay AJ, Puthenveedu MA, von Zastrow M, Jan YN, Jan LY. Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions. Cell. 2007;128:547–60.

    Article  CAS  PubMed  Google Scholar 

  94. Evans WH. Assembly of gap junction intercellular communication channels. Biochem Soc Trans. 1994;22:788–92.

    CAS  PubMed  Google Scholar 

  95. Musil LM, Goodenough DA. Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Cell. 1993;74:1065–77.

    Article  CAS  PubMed  Google Scholar 

  96. DeVries SH, Schwartz EA. Hemi-gap-junction channels in solitary horizontal cells of the catfish retina. J Physiol. 1992;445:201–30.

    CAS  PubMed  Google Scholar 

  97. Spray DC, Ye ZC, Ransom BR. Functional connexin ‘hemichannels’: a critical appraisal. Glia. 2006;54:758–73.

    Article  PubMed  Google Scholar 

  98. Quist AP, Rhee SK, Lin H, Lal R. Physiological role of gap-junctional hemichannels: extracellular calcium-dependent isomotic volume regulation. J Cell Biol. 2000;148:1063–10744.

    Article  CAS  PubMed  Google Scholar 

  99. Bruzzone S, Franco L, Guida L, Zocchi E, Contini P, Bisso A, Usai C, De Flora A. A self-restricted CD38-connexin 43 crosstalk affects NAD+ and cyclic ADP-ribose metabolism and regulates intracellular calcium in 3T3 fibroblasts. J Biol Chem. 2001;276:48300–8.

    Google Scholar 

  100. Bruzzone S, Guida L, Zocchi E, Franco L, De Flora A. Connexin 43 hemichannels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells. FASEB J. 2001;15:10–12.

    CAS  PubMed  Google Scholar 

  101. Boassa D, Ambrosi C, Qiu F, Dahl G, Gaietta G, Sosinsky G. Pannexin1 channels contain a glycosylation site that targets the hexamer to the plasma membrane. J Biol Chem. 2007;282:31733–43.

    Article  CAS  PubMed  Google Scholar 

  102. Penuela S, Bhalla R, Gong X-Q, Cowan K, Celetti S, BJ C, Bai D, Shao Q, Laird D. Pannexin1 and pannexin3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci. 2007;120:3772–83.

    Article  CAS  PubMed  Google Scholar 

  103. Locovei S, Bao L, Dahl G. Pannexin 1 in erythrocytes: function without a gap. Proc Natl Acad Sci USA. 2006;103:7655–9.

    Article  CAS  PubMed  Google Scholar 

  104. Preus D, Johnson R, Sheridan J, Meyer R. Analysis of gap junctions and formation plaques between reaggregating Novikoff hepatoma cells. J Ultrastr Res. 1981;77:263–76.

    Article  CAS  Google Scholar 

  105. Martin PE, Blundell G, Ahmad S, Errington RJ, Evans WH. Multiple pathways in the trafficking and assembly of connexin 26, 32 and 43 into gap junction intercellular communication channels. J Cell Sci. 2001;114:3845–55.

    CAS  PubMed  Google Scholar 

  106. Koval M, Harley JE, Hick E, Steinberg TH. Connexin46 is retained as monomers in a trans-Golgi compartment of osteoblastic cells. J Cell Biol. 1997;137:847–57.

    Article  CAS  PubMed  Google Scholar 

  107. Maza J, Mateescu M, Sarma JD, Koval M. Differential oligomerization of endoplasmic reticulum-retained connexin43/connexin32 chimeras. Cell Commun Adhes. 2003;10:319–22.

    CAS  PubMed  Google Scholar 

  108. Lal R, John SA, Laird DW, Arnsdorf MF. Heart gap junction preparations reveal hemiplaques by atomic force microscopy. Am J Physiol. 1995;268:C968-C977.

    CAS  PubMed  Google Scholar 

  109. Zampighi GA, Loo DD, Kreman M, Eskandari S, Wright EM. Functional and morphological correlates of connexin50 expressed in Xenopus laevis oocytes. J Gen Physiol. 1999;113:507–24.

    Article  CAS  PubMed  Google Scholar 

  110. Thomas MA, Huang S, Cokoja A, Riccio O, Staub O, Suter S, Chanson M. Interaction of connexins with protein partners in the control of channel turnover and gating. Biol Cell. 2002;94:445–56.

    Article  CAS  PubMed  Google Scholar 

  111. Xu X, Li WE, Huang GY, Meyer R, Chen T, Luo Y, Thomas MP, Radice GL, Lo CW. Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions. J Cell Biol. 2001;154:217–30.

    Article  CAS  PubMed  Google Scholar 

  112. Giepmans BN. Role of connexin43-interacting proteins at gap junctions. Adv Cardiol. 2006;42:41–56.

    Article  CAS  PubMed  Google Scholar 

  113. Giepmans BN. Gap junctions and connexin-interacting proteins. Cardiovasc Res. 2004;62:233–45.

    Article  CAS  PubMed  Google Scholar 

  114. Giepmans BNG, Moolenar WH. The gap junction protein connexin43 interacts with the second PDZ domains of the zona occludins-1 protein. Curr Biol. 1998;8:931–4.

    Article  CAS  PubMed  Google Scholar 

  115. Sosinsky GE, Solan JL, Gaietta GM, Ngan L, Lee GJ, Mackey MR, Lampe PD. The C-terminus of connexin43 adopts different conformations in the Golgi and gap junction as detected with structure-specific antibodies. Biochem J 2007 Dec 15;408:375-85.

    Article  PubMed  Google Scholar 

  116. Hunter AW, Barker RJ, Zhu C, Gourdie RG. Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell. 2005;16:5686–98.

    Article  CAS  PubMed  Google Scholar 

  117. Toyofuku T, Akamatsu Y, Zhang H, Kuzuya T, Tada M, Hori M. c-Src regulates the interaction between connexin-43 and ZO-1 in cardiac myocytes. J Biol Chem. 2001;276:1780–8.

    Article  CAS  PubMed  Google Scholar 

  118. van Zeijl L, Ponsioen B, Giepmans BN, Ariaens A, Postma FR, Varnai P, Balla T, Divecha N, Jalink K, Moolenaar WH. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. J Cell Biol. 2007;177:881–91.

    Article  PubMed  CAS  Google Scholar 

  119. Giepmans BN, Verlaan I, Hengeveld T, Janssen H, Calafat J, Falk MM, Moolenaar WH. Gap junction protein connexin-43 interacts directly with microtubules. Curr Biol. 2001;11:1364–8.

    Article  CAS  PubMed  Google Scholar 

  120. Butkevich E, Hulsmann S, Wenzel D, Shirao T, Duden R, Majoul I. Drebrin is a novel connexin-43 binding partner that links gap junctions to the submembrane cytoskeleton. Curr Biol. 2004;14:650–8.

    Article  CAS  PubMed  Google Scholar 

  121. Duffy HS, Delmar M, Spray DC. Formation of the gap junction nexus: binding partners for connexins. J Physiol Paris. 2002;96:243–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Dr. John Rash for generously providing the unpublished micrographs in Fig. 10.2 and for valuable discussions on channel packing. We also thank Tom Deerinck for supplying the image for Fig. 10.4. Support was contributed by National Science Foundation (NSF) grant MCB0543934, GM072881, and GM065937 (all to GES). Some of the work included here was conducted at the National Center for Microscopy and Imaging Research at San Diego, which is supported by National Institutes of Health (NIH) grant RR04050 awarded to Dr. Mark Ellisman.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Sosinsky, G.E., Gaietta, G.M., Giepmans, B.N. (2009). Gap Junction Morphology and Dynamics in Situ. In: Harris, A.L., Locke, D. (eds) Connexins. Humana Press. https://doi.org/10.1007/978-1-59745-489-6_10

Download citation

Publish with us

Policies and ethics