Gap junction trafficking and regulation (Homo sapiens)

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1-468126, 71291514101611115121317endoplasmic reticulum lumenperoxisomal matrixER-Golgi intermediate compartmentcytosolGolgi lumenmicrotubuleInvaginating gap junction plaquesJunctional channelCx26/Cx32ATPConnexin 32Cx43:ZO-1:c-src gap junctionConnexin 43 connexon in Golgi transport vesicleCx43:ZO-1c-srcDocked Cx43-containing transport vesiclesplanar gap junction plaquesplanar gap junction plaques associated with Dab2ADPZO-1gap junction plaqueConnexin 43Monomeric connexin proteinHemi-channelsConnexin 26 Connexonclosed Cx43 junctional channelConnexin 43 hemi-channelConnexin 26c-src-associated Cx43 junctional channelConnexin 32Connexon 26phospho-Y265 Cx43:ZO-1 gap junctionCx43 :ZO-1 gap junctionconnexons in Golgi transport vesicle docked to microtubulesCx26/Cx32Dab2DynaminPlanar gap junction plaques associated with Dab2 and DynaminConnexin 32 connexonConnexin 26:Connexin 32 connexonMyosin VIConnexin 43Connexin 43 connexonConnexin 26


Description

Gap junctions are clusters of intercellular channels connecting adjacent cells and permitting the direct exchange of ions and small molecules between cells. These channels are composed of two hemichannels, or connexons, one located on each of the two neighboring cells. Each connexon is composed of 6 trans-membrane protein subunits of the connexin (Cx) family. A gap of approximately 3 nm remains between the adjacent cell membranes, but two connexons interact and dock head-to-head in the extra-cellular space forming a tightly sealed, double-membrane intercellular channel (see Segretain and Falk, 2004). The activity of these intercellular channels is regulated, particularly by intramolecular modifications such as phosphorylation which appears to regulate connexin turnover, gap junction assembly and the opening and closure (gating) of gap junction channels.

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Bibliography

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  1. Segretain D, Falk MM.; ''Regulation of connexin biosynthesis, assembly, gap junction formation, and removal.''; PubMed Europe PMC
  2. Kelsell DP, Dunlop J, Hodgins MB.; ''Human diseases: clues to cracking the connexin code?''; PubMed Europe PMC
  3. Simon AM, Goodenough DA.; ''Diverse functions of vertebrate gap junctions.''; PubMed Europe PMC
  4. Bruzzone R.; ''Learning the language of cell-cell communication through connexin channels.''; PubMed Europe PMC
  5. Martin PE, Mambetisaeva ET, Archer DA, George CH, Evans WH.; ''Analysis of gap junction assembly using mutated connexins detected in Charcot-Marie-Tooth X-linked disease.''; PubMed Europe PMC
  6. Fishman GI, Moreno AP, Spray DC, Leinwand LA.; ''Functional analysis of human cardiac gap junction channel mutants.''; PubMed Europe PMC
  7. Falk MM, Kumar NM, Gilula NB.; ''Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins.''; PubMed Europe PMC
  8. 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.''; PubMed Europe PMC
  9. Wang M, Berthoud VM, Beyer EC.; ''Connexin43 increases the sensitivity of prostate cancer cells to TNFalpha-induced apoptosis.''; PubMed Europe PMC
  10. 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.''; PubMed Europe PMC
  11. Falk MM, Buehler LK, Kumar NM, Gilula NB.; ''Cell-free synthesis and assembly of connexins into functional gap junction membrane channels.''; PubMed Europe PMC
  12. Ahmad S, Diez JA, George CH, Evans WH.; ''Synthesis and assembly of connexins in vitro into homomeric and heteromeric functional gap junction hemichannels.''; PubMed Europe PMC
  13. Piehl M, Lehmann C, Gumpert A, Denizot JP, Segretain D, Falk MM.; ''Internalization of large double-membrane intercellular vesicles by a clathrin-dependent endocytic process.''; PubMed Europe PMC
  14. Spinella F, Rosanò L, Di Castro V, Nicotra MR, Natali PG, Bagnato A.; ''Endothelin-1 decreases gap junctional intercellular communication by inducing phosphorylation of connexin 43 in human ovarian carcinoma cells.''; PubMed Europe PMC
  15. 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.''; PubMed Europe PMC
  16. Huang S, Dudez T, Scerri I, Thomas MA, Giepmans BN, Suter S, Chanson M.; ''Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation.''; PubMed Europe PMC
  17. Wong RC, Pébay A, Nguyen LT, Koh KL, Pera MF.; ''Presence of functional gap junctions in human embryonic stem cells.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101632view11:49, 1 November 2018ReactomeTeamreactome version 66
101168view21:36, 31 October 2018ReactomeTeamreactome version 65
100694view20:09, 31 October 2018ReactomeTeamreactome version 64
100244view16:54, 31 October 2018ReactomeTeamreactome version 63
99796view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99346view12:48, 31 October 2018ReactomeTeamreactome version 62
94003view13:50, 16 August 2017ReactomeTeamreactome version 61
93615view11:28, 9 August 2017ReactomeTeamreactome version 61
87452view13:58, 22 July 2016MkutmonOntology Term : 'transport pathway' added !
86723view09:24, 11 July 2016ReactomeTeamreactome version 56
83093view09:58, 18 November 2015ReactomeTeamVersion54
81417view12:56, 21 August 2015ReactomeTeamVersion53
76886view08:15, 17 July 2014ReactomeTeamFixed remaining interactions
76591view11:57, 16 July 2014ReactomeTeamFixed remaining interactions
75923view09:57, 11 June 2014ReactomeTeamRe-fixing comment source
75624view10:49, 10 June 2014ReactomeTeamReactome 48 Update
74979view13:50, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74623view08:40, 30 April 2014ReactomeTeamReactome46
68979view17:42, 8 July 2013MaintBotUpdated to 2013 gpml schema
42043view21:52, 4 March 2011MaintBotAutomatic update
39846view05:52, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Connexin

43

ProteinP17302 (UniProt)
Connexin 26 ProteinP29033 (UniProt)
Connexin 26

Connexon

ComplexREACT_21620 (Reactome)
Connexin 26:

Connexin 32 connexon

ComplexREACT_9762 (Reactome)
Connexin 32 ProteinP08034 (UniProt)
Connexin 32

connexon

ComplexREACT_9765 (Reactome)
Connexin 43 ProteinP17302 (UniProt)
Connexin 43

connexon

ComplexREACT_9901 (Reactome)
Connexin 43

connexon in Golgi transport vesicle

ComplexREACT_10502 (Reactome)
Connexin 43 hemi-

channel

ComplexREACT_10289 (Reactome)
Connexon 26 ComplexREACT_10376 (Reactome)
Cx26/Cx32 ProteinREACT_9641 (Reactome)
Cx26/Cx32 ProteinREACT_9706 (Reactome)
Cx43 :ZO-1 gap

junction

ComplexREACT_10329 (Reactome)
Cx43:ZO-1 ComplexREACT_10187 (Reactome)
Cx43:ZO-1:c-src

gap junction

ComplexREACT_10511 (Reactome)
Dab2 ProteinREACT_10839 (Reactome)
Docked Cx43-

containing transport vesicles

ComplexREACT_10422 (Reactome)
Dynamin ProteinREACT_10614 (Reactome)
Hemi-

channels

ComplexREACT_10652 (Reactome)
Invaginating gap

junction plaques

ComplexREACT_10333 (Reactome)
Junctional

channel

ComplexREACT_10244 (Reactome)
Monomeric

connexin protein

ProteinREACT_9675 (Reactome)
Myosin

VI

ProteinREACT_10786 (Reactome)
Planar gap junction

plaques associated with Dab2 and Dynamin

ComplexREACT_10413 (Reactome)
ZO-1 ProteinREACT_10984 (Reactome)
c-src ProteinP12931-2 (UniProt)
c-src-associated

Cx43 junctional channel

ComplexREACT_10199 (Reactome)
closed Cx43

junctional channel

ComplexREACT_10597 (Reactome)
connexons in Golgi

transport vesicle docked to microtubules

ComplexREACT_10450 (Reactome)
gap junction

plaque

ComplexREACT_10558 (Reactome)
microtubule UnknownREACT_10446 (Reactome)
phospho-Y265

Cx43:ZO-1 gap junction

ComplexREACT_10386 (Reactome)
planar gap junction

plaques

ComplexREACT_10866 (Reactome)
planar gap junction

plaques associated with Dab2

ComplexREACT_10755 (Reactome)

Annotated Interactions

No annotated interactions

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