title: Mechanisms of gap junction traffic in health and disease.
abstract: Gap junctions (GJs) allow direct communication between cells. In the heart, GJs mediate the electrical coupling of cardiomyocytes and as such dictate the speed and direction of cardiac conduction. A prominent feature of acquired structural heart disease is remodeling of GJ protein expression and localization concomitant with increased susceptibility to lethal arrhythmias, leading many to hypothesize that the two are causally linked. Detailed understanding of the cellular mechanisms that regulate GJ localization and function within cardiomyocytes may therefore uncover potential therapeutic strategies for a significant clinical problem. This review will outline our current understanding of GJ cell biology with the intent of highlighting cellular mechanisms responsible for GJ remodeling associated with cardiac disease.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Geoffrey G
authors.initials: GG
authors.lastname: Hesketh
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Van Eyk
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D017630:Connexins / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D006329:Heart Conduction System / Q000502:physiology; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs
chemical_list: D017630:Connexins
references.citation: Circ Res. 2004 Feb 6;94(2):215-22
references.pmid: 14699011
references.citation: J Cell Biol. 2002 Apr 29;157(3):381-94
references.pmid: 11980915
references.citation: Curr Biol. 2001 Sep 4;11(17):1364-8
references.pmid: 11553331
references.citation: J Biol Chem. 2005 May 20;280(20):19925-36
references.pmid: 15741167
references.citation: J Mol Cell Cardiol. 2008 Mar;44(3):597-606
references.pmid: 18201716
references.citation: Mol Biol Cell. 1992 Aug;3(8):865-74
references.pmid: 1327298
references.citation: Science. 1995 Mar 24;267(5205):1831-4
references.pmid: 7892609
references.citation: J Cell Sci. 2008 Dec 15;121(Pt 24):4069-78
references.pmid: 19033388
references.citation: J Cell Sci. 2004 Apr 15;117(Pt 10):2087-96
references.pmid: 15054109
references.citation: Am J Physiol Cell Physiol. 2003 Feb;284(2):C511-20
references.pmid: 12388103
references.citation: Mol Cell Biol. 2007 Nov;27(21):7522-37
references.pmid: 17785437
references.citation: Science. 1988 Jan 22;239(4838):398-401
references.pmid: 2447651
references.citation: J Cell Biol. 2007 Dec 17;179(6):1301-9
references.pmid: 18086922
references.citation: J Cell Physiol. 2002 Dec;193(3):373-9
references.pmid: 12384989
references.citation: J Biol Chem. 2001 Mar 16;276(11):8544-9
references.pmid: 11124251
references.citation: Neurobiol Dis. 2002 Oct;11(1):43-52
references.pmid: 12460545
references.citation: Mol Biol Cell. 2003 Jun;14(6):2470-81
references.pmid: 12808044
references.citation: Cell Commun Adhes. 2001;8(4-6):219-23
references.pmid: 12064592
references.citation: Biochim Biophys Acta. 2005 Jun 10;1711(2):172-82
references.pmid: 15955302
references.citation: Circ Res. 2002 Oct 4;91(7):640-7
references.pmid: 12364393
references.citation: J Biol Chem. 2004 Dec 24;279(52):54695-701
references.pmid: 15492000
references.citation: J Cell Sci. 2004 Mar 1;117(Pt 7):1211-20
references.pmid: 14970263
references.citation: J Biol Chem. 2003 May 16;278(20):18682-8
references.pmid: 12637502
references.citation: J Cell Biol. 2007 Jun 4;177(5):881-91
references.pmid: 17535964
references.citation: Cell Commun Adhes. 2008 May;15(1):65-74
references.pmid: 18649179
references.citation: Biochem J. 2006 Jan 1;393(Pt 1):59-67
references.pmid: 16162097
references.citation: Cell Commun Adhes. 2003 Jul-Dec;10(4-6):329-33
references.pmid: 14681037
references.citation: Exp Cell Res. 1997 Nov 1;236(2):482-92
references.pmid: 9367633
references.citation: J Cell Mol Med. 2001 Oct-Dec;5(4):355-66
references.pmid: 12067469
references.citation: Science. 2002 Apr 19;296(5567):503-7
references.pmid: 11964472
references.citation: Cardiovasc Pathol. 2007 May-Jun;16(3):159-64
references.pmid: 17502245
references.citation: Circ Res. 2004 Oct 1;95(7):717-25
references.pmid: 15345654
references.citation: J Cell Sci. 2005 Oct 1;118(Pt 19):4451-62
references.pmid: 16159960
references.citation: Cell Commun Adhes. 2007 Sep-Oct;14(5):211-26
references.pmid: 18163231
references.citation: J Cell Sci. 2001 Mar;114(Pt 6):1229-35
references.pmid: 11228166
references.citation: Circ Res. 2005 Sep 2;97(5):474-81
references.pmid: 16100040
references.citation: J Cell Sci. 1995 Sep;108 ( Pt 9):3079-90
references.pmid: 8537447
references.citation: Circ Res. 1998 Jul 13;83(1):27-32
references.pmid: 9670915
references.citation: Cell Regul. 1990 Dec;1(13):989-1002
references.pmid: 1966893
references.citation: Heart Rhythm. 2004 May;1(1):3-11
references.pmid: 15851108
references.citation: Mol Cell Biol. 1990 Apr;10(4):1754-63
references.pmid: 1690850
references.citation: Cell Commun Adhes. 2008 May;15(1):75-84
references.pmid: 18649180
references.citation: J Biol Chem. 1998 May 22;273(21):12725-31
references.pmid: 9582296
references.citation: J Biol Chem. 2002 Jun 7;277(23):20911-8
references.pmid: 11929864
references.citation: Circ Res. 2002 Feb 22;90(3):317-24
references.pmid: 11861421
references.citation: Dev Biol. 1996 Oct 10;179(1):1-16
references.pmid: 8873750
references.citation: Am J Physiol Heart Circ Physiol. 2004 May;286(5):H2001-9
references.pmid: 14704225
references.citation: J Cell Sci. 2000 Sep;113 ( Pt 17):3037-49
references.pmid: 10934042
references.citation: Prog Biophys Mol Biol. 2007 May-Jun;94(1-2):107-19
references.pmid: 17507079
references.citation: Circ Res. 1999 Oct 15;85(8):672-81
references.pmid: 10521240
references.citation: Mol Biol Cell. 2000 Jun;11(6):1933-46
references.pmid: 10848620
references.citation: Cell. 2007 Feb 9;128(3):547-60
references.pmid: 17289573
references.citation: Cardiovasc Res. 2008 Oct 1;80(1):9-19
references.pmid: 18519446
references.citation: Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1762-70
references.pmid: 15205174
references.citation: J Cell Biol. 2001 Aug 20;154(4):815-27
references.pmid: 11514593
references.citation: Cardiovasc Res. 2008 Mar 1;77(4):757-65
references.pmid: 18056766
references.citation: J Biol Chem. 1996 Feb 16;271(7):3779-86
references.pmid: 8631994
references.citation: FEBS Lett. 2008 Aug 20;582(19):2887-92
references.pmid: 18656476
references.citation: J Cell Sci. 2003 Jun 1;116(Pt 11):2213-22
references.pmid: 12730291
references.citation: Eur J Neurosci. 2004 Apr;19(8):2132-46
references.pmid: 15090040
references.citation: FEBS Lett. 2008 Dec 10;582(29):4039-46
references.pmid: 18992245
references.citation: Neuron. 2005 Jun 2;46(5):731-44
references.pmid: 15924860
references.citation: J Biol Chem. 2002 Mar 22;277(12):10482-8
references.pmid: 11790776
references.citation: J Cell Biol. 1986 Sep;103(3):755-66
references.pmid: 3528172
references.citation: Cardiovasc Res. 2005 Aug 15;67(3):539-47
references.pmid: 15913582
references.citation: J Cell Biol. 1999 Mar 8;144(5):1033-45
references.pmid: 10085299
references.citation: J Biol Chem. 2003 Aug 8;278(32):30005-14
references.pmid: 12767974
references.citation: Mol Biol Cell. 1999 Jun;10(6):2033-50
references.pmid: 10359613
references.citation: J Cell Sci. 2006 Sep 1;119(Pt 17):3634-42
references.pmid: 16931598
references.citation: Neuroscience. 2004;126(3):611-30
references.pmid: 15183511
references.citation: J Biol Chem. 2008 Feb 29;283(9):5748-59
references.pmid: 18079109
references.citation: FEBS Lett. 2002 Nov 6;531(2):132-6
references.pmid: 12417300
references.citation: J Cell Biol. 1979 Dec;83(3):576-87
references.pmid: 574870
references.citation: Biochem J. 2006 Mar 15;394(Pt 3):527-43
references.pmid: 16492141
references.citation: J Clin Invest. 1997 Apr 15;99(8):1991-8
references.pmid: 9109444
references.citation: Biochem Biophys Res Commun. 2008 Oct 3;374(4):679-82
references.pmid: 18675253
references.citation: Mol Biol Cell. 2005 Nov;16(11):5247-57
references.pmid: 16135529
references.citation: J Biol Chem. 1998 Apr 10;273(15):9188-96
references.pmid: 9535909
references.citation: Nat Clin Pract Cardiovasc Med. 2008 May;5(5):258-67
references.pmid: 18382419
references.citation: Q Rev Biophys. 2001 Aug;34(3):325-472
references.pmid: 11838236
references.citation: J Biol Chem. 1995 May 26;270(21):12751-61
references.pmid: 7539006
references.citation: J Biol Chem. 2001 Jan 19;276(3):1780-8
references.pmid: 11035005
references.citation: Circ Res. 1996 Oct;79(4):647-58
references.pmid: 8831488
references.citation: Exp Cell Res. 2002 Apr 15;275(1):67-80
references.pmid: 11925106
references.citation: J Biol Chem. 1999 Apr 9;274(15):10489-96
references.pmid: 10187840
references.citation: Heart Rhythm. 2007 Sep;4(9):1196-205
references.pmid: 17765621
references.citation: Circ Res. 2007 Dec 7;101(12):1283-91
references.pmid: 17932323
references.citation: J Membr Biol. 1995 Dec;148(3):243-53
references.pmid: 8747556
references.citation: Curr Biol. 2004 Apr 20;14(8):650-8
references.pmid: 15084279
references.citation: J Biol Chem. 2000 Aug 18;275(33):25207-15
references.pmid: 10940315
references.citation: Nature. 2009 Apr 2;458(7238):597-602
references.pmid: 19340074
references.citation: J Biol Chem. 2001 Jun 22;276(25):23051-5
references.pmid: 11313345
references.citation: Trends Cell Biol. 2006 Mar;16(3):159-66
references.pmid: 16490353
references.citation: J Biol Chem. 1997 Sep 5;272(36):22824-31
references.pmid: 9278444
references.citation: Heart Rhythm. 2008 Dec;5(12):1715-23
references.pmid: 19084810
references.citation: J Biol Chem. 2005 Mar 25;280(12):11458-66
references.pmid: 15644317
references.citation: Biochem Biophys Res Commun. 2007 Dec 14;364(2):313-7
references.pmid: 17945186
references.citation: Cell Commun Adhes. 2003 Jul-Dec;10(4-6):211-4
references.pmid: 14681018
references.citation: J Cell Biol. 2000 Jun 26;149(7):1503-12
references.pmid: 10871288
references.citation: Mol Biol Cell. 2007 Feb;18(2):337-47
references.pmid: 17108328
references.citation: Curr Biol. 1998 Jul 30-Aug 13;8(16):931-4
references.pmid: 9707407
references.citation: J Biol Chem. 1995 Nov 3;270(44):26399-403
references.pmid: 7592854
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12545-50
references.pmid: 18719117
references.citation: Eur J Cell Biol. 1999 Dec;78(12):856-66
references.pmid: 10669104
references.citation: Biochim Biophys Acta. 2005 Jun 10;1711(2):154-63
references.pmid: 15955300
references.citation: J Cell Biol. 1998 Mar 9;140(5):1199-209
references.pmid: 9490732
references.citation: N Engl J Med. 2009 Mar 12;360(11):1075-84
references.pmid: 19279339
references.citation: Biol Chem. 2006 Sep;387(9):1227-36
references.pmid: 16972791
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10446-51
references.pmid: 12149451
references.citation: Biochemistry. 2005 Feb 22;44(7):2385-96
references.pmid: 15709751
references.citation: Protein Sci. 2006 Oct;15(10):2344-55
references.pmid: 17008717
references.citation: Circ Res. 2001 Feb 16;88(3):333-9
references.pmid: 11179202
references.citation: J Membr Biol. 2007 Aug;218(1-3):65-71
references.pmid: 17585361
references.citation: Nat Rev Mol Cell Biol. 2003 Apr;4(4):285-94
references.pmid: 12671651
references.citation: J Biol Chem. 2003 Mar 7;278(10):8326-32
references.pmid: 12506110
references.citation: Mol Biol Cell. 2005 Dec;16(12):5686-98
references.pmid: 16195341
references.citation: Circ Res. 2009 May 8;104(9):1103-12
references.pmid: 19342602
references.citation: Circ Res. 2007 Sep 28;101(7):703-11
references.pmid: 17673670
references.citation: Cell. 1993 Sep 24;74(6):1065-77
references.pmid: 7691412