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PMID: 8844328 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The life cycle of a connexin: gap junction formation, removal, and degradation.

Journal of bioenergetics and biomembranes ·Vol. 28 ·No. 4 ·1996-08-00 ·Pages 311-8

Laird DW

Abstract

Gap junction proteins, connexins, possess many properties that are atypical of other well-characterized integral membrane proteins. Oligomerization of connexins into hemichannels (connexons) has been shown to occur after the protein exits the endoplasmic reticulum. Once delivered to the cell surface, connexons from one cell pair with connexons from a neighboring cell, a process that is facilitated by calcium-dependent cell adhesion molecules. Channels cluster into defined plasma membrane domains to form plaques. Unexpectedly, gap junctions are not stable (half-life < 5 h) and are thought to be retrieved back into the cell in the form of double membrane structures when one cell internalizes the entire gap junction through endocytosis. Evidence exists for both proteasomal and lysosomal degradation of gap junctions, and it remains possible that both mechanisms are involved in connexin degradation. In addition to opening and closing of gap junction channels (gating), the formation and removal of gap junctions play an essential role in regulating the level of intercellular communication.

MeSH Terms
Animals Biological Transport Connexins/physiology Gap Junctions/physiology Humans Ion Channel Gating Ion Channels/physiology
Chemicals
Connexins Ion Channels
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Laird D W
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
References (51)
51 references, click to expand
  1. Connexin43: a protein from rat heart homologous to a gap junction protein from liver.
    J Cell Biol. 1987 Dec;105(6 Pt 1):2621-9 PMID: 2826492
  2. Hexagonal array of subunits in intercellular junctions of the mouse heart and liver.
    J Cell Biol. 1967 Jun;33(3):C7-C12 PMID: 6036535
  3. Topography of connexin32 in rat liver gap junctions. Evidence for an intramolecular disulphide linkage connecting the two extracellular peptide loops.
    J Cell Sci. 1991 Nov;100 ( Pt 3):567-78 PMID: 1667015
  4. Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins.
    J Cell Biol. 1994 Oct;127(2):343-55 PMID: 7929580
  5. Immunolocalization of an extracellular domain of connexin43 in rat heart gap junctions.
    Eur J Cell Biol. 1991 Dec;56(2):391-400 PMID: 1724962
  6. Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain.
    J Biol Chem. 1993 Jul 5;268(19):14294-300 PMID: 8390988
  7. Biochemical and immunochemical analysis of the arrangement of connexin43 in rat heart gap junction membranes.
    J Cell Sci. 1990 Sep;97 ( Pt 1):109-17 PMID: 2175311
  8. THE OCCURRENCE OF A SUBUNIT PATTERN IN THE UNIT MEMBRANES OF CLUB ENDINGS IN MAUTHNER CELL SYNAPSES IN GOLDFISH BRAINS.
    J Cell Biol. 1963 Oct;19:201-21 PMID: 14069795
  9. Assembly of hepatic gap junctions. Topography and distribution of connexin 32 in intracellular and plasma membranes determined using sequence-specific antibodies.
    J Biol Chem. 1993 Jan 15;268(2):1260-5 PMID: 8380409
  10. The gap junction protein connexin43 is degraded via the ubiquitin proteasome pathway.
    J Biol Chem. 1995 Nov 3;270(44):26399-403 PMID: 7592854
  11. Connexon integrity is maintained by non-covalent bonds: intramolecular disulfide bonds link the extracellular domains in rat connexin-43.
    Biochem Biophys Res Commun. 1991 Aug 15;178(3):1312-8 PMID: 1651718
  12. Trapping an intermediate form of connexin43 in the Golgi.
    Exp Cell Res. 1993 May;206(1):85-92 PMID: 8387024
  13. Characterization of gap junctional communication-deficient mutants of a rat liver epithelial cell line.
    Eur J Cell Biol. 1993 Apr;60(2):250-5 PMID: 7687215
  14. Modulation of cell junctions during differentiation of the chicken otocyst sensory epithelium.
    Dev Biol. 1979 Jan;68(1):110-29 PMID: 437313
  15. Topology of the Mr 27,000 liver gap junction protein. Cytoplasmic localization of amino- and carboxyl termini and a hydrophilic domain which is protease-hypersensitive.
    J Biol Chem. 1988 Dec 15;263(35):19105-11 PMID: 2848816
  16. Expression of the gap junction protein connexin43 in embryonic chick lens: molecular cloning, ultrastructural localization, and post-translational phosphorylation.
    J Membr Biol. 1990 Jun;116(2):163-75 PMID: 2166164
  17. Gap junctions and cell polarity: connexin32 and connexin43 expressed in polarized thyroid epithelial cells assemble into separate gap junctions, which are located in distinct regions of the lateral plasma membrane domain.
    J Cell Sci. 1995 Jul;108 ( Pt 7):2609-17 PMID: 7593302
  18. Topology of the 32-kd liver gap junction protein determined by site-directed antibody localizations.
    EMBO J. 1988 Oct;7(10):2967-75 PMID: 2460334
  19. The gap junction proteins beta 1-connexin (connexin-32) and beta 2-connexin (connexin-26) can form heteromeric hemichannels.
    J Biol Chem. 1995 Mar 24;270(12 ):6768-72 PMID: 7896822
  20. Gap junction turnover, intracellular trafficking, and phosphorylation of connexin43 in brefeldin A-treated rat mammary tumor cells.
    J Cell Biol. 1995 Dec;131(5):1193-203 PMID: 8522583
  21. Gap junctions between cultured astrocytes: immunocytochemical, molecular, and electrophysiological analysis.
    J Neurosci. 1991 May;11(5):1421-32 PMID: 1851221
  22. Structure of the extracellular surface of the gap junction by atomic force microscopy.
    Biophys J. 1993 Jul;65(1):149-63 PMID: 8396452
  23. Inhibition of gap junction and adherens junction assembly by connexin and A-CAM antibodies.
    J Cell Biol. 1992 Oct;119(1):179-89 PMID: 1326565
  24. Cell-, age- and stage-dependent distribution of connexin43 gap junctions in testes.
    J Cell Sci. 1992 Sep;103 ( Pt 1):81-96 PMID: 1331136
  25. Heteromeric connexons in lens gap junction channels.
    Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1287-91 PMID: 8577756
  26. Gap junction formation between reaggregated Novikoff hepatoma cells.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4536-40 PMID: 4373716
  27. Myometrial connexin 43 trafficking and gap junction assembly at term and in preterm labor.
    Mol Reprod Dev. 1992 Sep;33(1):27-38 PMID: 1324698
  28. Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques.
    J Cell Biol. 1991 Dec;115(5):1357-74 PMID: 1659577
  29. Mixing of connexins in gap junction membrane channels.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9210-4 PMID: 7568103
  30. Mutational analysis of gap junction formation.
    Biophys J. 1992 Apr;62(1):172-80; discussion 180-2 PMID: 1376165
  31. Differential phosphorylation of the gap junction protein connexin43 in junctional communication-competent and -deficient cell lines.
    J Cell Biol. 1990 Nov;111(5 Pt 1):2077-88 PMID: 2172261
  32. Atomic force microscopy and dissection of gap junctions.
    Science. 1991 Sep 20;253(5026):1405-8 PMID: 1910206
  33. Molecular cloning and characterization of a new member of the gap junction gene family, connexin-31.
    J Biol Chem. 1991 Apr 5;266(10 ):6524-31 PMID: 1706719
  34. Antisera directed against connexin43 peptides react with a 43-kD protein localized to gap junctions in myocardium and other tissues.
    J Cell Biol. 1989 Feb;108(2):595-605 PMID: 2537319
  35. The 43-kD polypeptide of heart gap junctions: immunolocalization, topology, and functional domains.
    J Cell Biol. 1989 Jun;108(6):2241-54 PMID: 2472402
  36. Five-hour half-life of mouse liver gap-junction protein.
    J Cell Biol. 1981 Aug;90(2):521-6 PMID: 7287816
  37. Protein oligomerization in the endoplasmic reticulum.
    Annu Rev Cell Biol. 1989;5:277-307 PMID: 2688707
  38. Control of protein exit from the endoplasmic reticulum.
    Annu Rev Cell Biol. 1989;5:1-23 PMID: 2688704
  39. Gap junction structures. II. Analysis of the x-ray diffraction data.
    J Cell Biol. 1977 Aug;74(2):629-45 PMID: 889612
  40. Gap junction assembly and endocytosis correlated with patterns of growth in a cultured adrenocortical tumor cell (SW-13).
    Cancer Res. 1981 Oct;41(10):4063-74 PMID: 7285014
  41. Ultrastructural analysis of gap junctions in C6 glioma cells transfected with connexin43 cDNA.
    Exp Cell Res. 1993 May;206(1):72-84 PMID: 8387023
  42. Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER.
    Cell. 1993 Sep 24;74(6):1065-77 PMID: 7691412
  43. Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin.
    J Cell Biol. 1991 Aug;114(3):545-55 PMID: 1650371
  44. A fine structural analysis of intercellular junctions in the mouse liver.
    J Cell Biol. 1970 May;45(2):272-90 PMID: 4105112
  45. Phosphorylation of connexin43 gap junction protein in uninfected and Rous sarcoma virus-transformed mammalian fibroblasts.
    Mol Cell Biol. 1990 Apr;10(4):1754-63 PMID: 1690850
  46. Heart gap junction preparations reveal hemiplaques by atomic force microscopy.
    Am J Physiol. 1995 Apr;268(4 Pt 1):C968-77 PMID: 7733245
  47. Origin and fate of cytoplasmic gap junctional vesicles in rabbit granulosa cells.
    Tissue Cell. 1978;10(3):585-98 PMID: 725913
  48. Turnover and phosphorylation dynamics of connexin43 gap junction protein in cultured cardiac myocytes.
    Biochem J. 1991 Jan 1;273(Pt 1):67-72 PMID: 1846532
  49. Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly.
    J Cell Biol. 1994 Dec;127(6 Pt 2):1895-905 PMID: 7806568
  50. Cyclic adenosine monophosphate stimulates biosynthesis and phosphorylation of the 26 kDa gap junction protein in cultured mouse hepatocytes.
    Eur J Cell Biol. 1987 Feb;43(1):48-54 PMID: 3032632
  51. Evidence for the participation of actin microfilaments and bristle coats in the internalization of gap junction membrane.
    J Cell Biol. 1979 Dec;83(3):576-87 PMID: 574870
Article Info
Journal
Journal of bioenergetics and biomembranes
Abbr.
J Bioenerg Biomembr
ISSN
0145-479X
DOI
10.1007/BF02110107
Published
1996-08-00
Pages
311-8
Language
English
Region
United States
NLM ID
7701859
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02110107 View journal details
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