Gap junction trafficking and regulation (Homo sapiens)

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8, 11, 16, 171512139131434, 56224131107cytosolER-Golgi intermediate compartmentGolgi lumenendoplasmic reticulum lumenperoxisomal matrixconnexons in Golgi transport vesicle docked to microtubulesConnexin 32Junctional channelCx43:ZO-1:c-src gap junctionConnexin 32 connexongap junction plaqueConnexin 26ZO-1Connexin 32Hemi-channelsConnexin 26:Connexin 32 connexonphospho-Y265 Cx43:ZO-1 gap junctionplanar gap junction plaquesConnexin 43 connexonADPplanar gap junction plaques associated with Dab2Connexin 43 hemi-channelConnexin 43c-srcCx43:ZO-1Cx26/Cx32Connexin 26 ConnexonMyosin VIMonomeric connexin proteinATPInvaginating gap junction plaquesCx43 :ZO-1 gap junctionc-src-associated Cx43 junctional channelConnexon 26Docked Cx43-containing transport vesiclesCx26/Cx32closed Cx43 junctional channelmicrotubuleDab2Connexin 43 connexon in Golgi transport vesicleDynaminPlanar gap junction plaques associated with Dab2 and DynaminConnexin 26Connexin 43


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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  1. 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 Scholia
  2. 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 Scholia
  3. Wong RC, Pébay A, Nguyen LT, Koh KL, Pera MF.; ''Presence of functional gap junctions in human embryonic stem cells.''; PubMed Europe PMC Scholia
  4. Simon AM, Goodenough DA.; ''Diverse functions of vertebrate gap junctions.''; PubMed Europe PMC Scholia
  5. Segretain D, Falk MM.; ''Regulation of connexin biosynthesis, assembly, gap junction formation, and removal.''; PubMed Europe PMC Scholia
  6. Fishman GI, Moreno AP, Spray DC, Leinwand LA.; ''Functional analysis of human cardiac gap junction channel mutants.''; PubMed Europe PMC Scholia
  7. Wang M, Berthoud VM, Beyer EC.; ''Connexin43 increases the sensitivity of prostate cancer cells to TNFalpha-induced apoptosis.''; PubMed Europe PMC Scholia
  8. 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 Scholia
  9. 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 Scholia
  10. 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 Scholia
  11. Bruzzone R.; ''Learning the language of cell-cell communication through connexin channels.''; PubMed Europe PMC Scholia
  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 Scholia
  13. Kelsell DP, Dunlop J, Hodgins MB.; ''Human diseases: clues to cracking the connexin code?''; PubMed Europe PMC Scholia
  14. 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 Scholia
  15. 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 Scholia
  16. Falk MM, Kumar NM, Gilula NB.; ''Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins.''; PubMed Europe PMC Scholia
  17. Falk MM, Buehler LK, Kumar NM, Gilula NB.; ''Cell-free synthesis and assembly of connexins into functional gap junction membrane channels.''; PubMed Europe PMC Scholia


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External references


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


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


ComplexREACT_21620 (Reactome)
Connexin 26:

Connexin 32 connexon

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


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


ComplexREACT_9901 (Reactome)
Connexin 43

connexon in Golgi transport vesicle

ComplexREACT_10502 (Reactome)
Connexin 43 hemi-


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


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

gap junction

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

containing transport vesicles

ComplexREACT_10422 (Reactome)
Dynamin ProteinREACT_10614 (Reactome)


ComplexREACT_10652 (Reactome)
Invaginating gap

junction plaques

ComplexREACT_10333 (Reactome)


ComplexREACT_10244 (Reactome)

connexin protein

ProteinREACT_9675 (Reactome)


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)

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


ComplexREACT_10558 (Reactome)
microtubule REACT_10446 (Reactome)

Cx43:ZO-1 gap junction

ComplexREACT_10386 (Reactome)
planar gap junction


ComplexREACT_10866 (Reactome)
planar gap junction

plaques associated with Dab2

ComplexREACT_10755 (Reactome)

Annotated Interactions

No annotated interactions

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