Gap junction trafficking and regulation (Homo sapiens)
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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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- Bruzzone R.; ''Learning the language of cell-cell communication through connexin channels.''; PubMed Europe PMC Scholia
- 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
- 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
- Segretain D, Falk MM.; ''Regulation of connexin biosynthesis, assembly, gap junction formation, and removal.''; PubMed Europe PMC Scholia
- 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
- 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
- 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
- Kelsell DP, Dunlop J, Hodgins MB.; ''Human diseases: clues to cracking the connexin code?''; PubMed Europe PMC Scholia
- 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
- 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
- Falk MM, Kumar NM, Gilula NB.; ''Membrane insertion of gap junction connexins: polytopic channel forming membrane proteins.''; PubMed Europe PMC Scholia
- 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
- Wang M, Berthoud VM, Beyer EC.; ''Connexin43 increases the sensitivity of prostate cancer cells to TNFalpha-induced apoptosis.''; PubMed Europe PMC Scholia
- Simon AM, Goodenough DA.; ''Diverse functions of vertebrate gap junctions.''; PubMed Europe PMC Scholia
- 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
- Fishman GI, Moreno AP, Spray DC, Leinwand LA.; ''Functional analysis of human cardiac gap junction channel mutants.''; PubMed Europe PMC Scholia
- Wong RC, Pébay A, Nguyen LT, Koh KL, Pera MF.; ''Presence of functional gap junctions in human embryonic stem cells.''; PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ADP | Metabolite | 16761 (ChEBI) | |
ATP | Metabolite | 15422 (ChEBI) | |
Connexin
43 | Protein | P17302 (UniProt) | |
Connexin 26 | Protein | P29033 (UniProt) | |
Connexin 26
Connexon | Complex | REACT_21620 (Reactome) | |
Connexin 26:
Connexin 32 connexon | Complex | REACT_9762 (Reactome) | |
Connexin 32 | Protein | P08034 (UniProt) | |
Connexin 32
connexon | Complex | REACT_9765 (Reactome) | |
Connexin 43 | Protein | P17302 (UniProt) | |
Connexin 43
connexon | Complex | REACT_9901 (Reactome) | |
Connexin 43
connexon in Golgi transport vesicle | Complex | REACT_10502 (Reactome) | |
Connexin 43 hemi-
channel | Complex | REACT_10289 (Reactome) | |
Connexon 26 | Complex | REACT_10376 (Reactome) | |
Cx26/Cx32 | Protein | REACT_9641 (Reactome) | |
Cx26/Cx32 | Protein | REACT_9706 (Reactome) | |
Cx43 :ZO-1 gap
junction | Complex | REACT_10329 (Reactome) | |
Cx43:ZO-1 | Complex | REACT_10187 (Reactome) | |
Cx43:ZO-1:c-src
gap junction | Complex | REACT_10511 (Reactome) | |
Dab2 | Protein | REACT_10839 (Reactome) | |
Docked Cx43-
containing transport vesicles | Complex | REACT_10422 (Reactome) | |
Dynamin | Protein | REACT_10614 (Reactome) | |
Hemi-
channels | Complex | REACT_10652 (Reactome) | |
Invaginating gap
junction plaques | Complex | REACT_10333 (Reactome) | |
Junctional
channel | Complex | REACT_10244 (Reactome) | |
Monomeric
connexin protein | Protein | REACT_9675 (Reactome) | |
Myosin
VI | Protein | REACT_10786 (Reactome) | |
Planar gap junction
plaques associated with Dab2 and Dynamin | Complex | REACT_10413 (Reactome) | |
ZO-1 | Protein | REACT_10984 (Reactome) | |
c-src | Protein | P12931-2 (UniProt) | |
c-src-associated
Cx43 junctional channel | Complex | REACT_10199 (Reactome) | |
closed Cx43
junctional channel | Complex | REACT_10597 (Reactome) | |
connexons in Golgi
transport vesicle docked to microtubules | Complex | REACT_10450 (Reactome) | |
gap junction
plaque | Complex | REACT_10558 (Reactome) | |
microtubule | Unknown | REACT_10446 (Reactome) | |
phospho-Y265
Cx43:ZO-1 gap junction | Complex | REACT_10386 (Reactome) | |
planar gap junction
plaques | Complex | REACT_10866 (Reactome) | |
planar gap junction
plaques associated with Dab2 | Complex | REACT_10755 (Reactome) |
Annotated Interactions
No annotated interactions