Gap junction trafficking and regulation (Homo sapiens)

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1-41413615717111613105815137, 129endoplasmic reticulum-Golgi intermediate compartmentGolgi lumenlysosomal membranecytosolendoplasmic reticulum lumenGJC1 SRC-2 phospho-Y265Cx43:ZO-1 gapjunctionGJD3 Microtubule protofilament CLTA F-actin closed Cx43junctional channelJunctional channelGJA1 Cx26/Cx32GJA1 p-Y265-GJA1 GJA9 GJA3 CLTB SRC-2GJB6 GJA4 F-actin Connexon 26AP2M1 Cx43:ZO-1:c-src gapjunctionF-actin c-src-associatedCx43 junctionalchannelGJA1 F-actin GJA5 GJA1 gap junction plaquePlanar gap junctionplaques associatedwith Dab2 andDynaminGJB2 TJP1 Microtubule protofilament p-Y265-GJA1 DNM2 CLTC MYO6DAB2 GJD2 GJB2GJB1 mRNACLTCL1 Microtubule protofilament GJB2 p-Y265-GJA1 GJA8 GJA1 Hemi-channelsGJB2 GJB7 connexons in Golgitransport vesicledocked tomicrotubulesDAB2GJB1DNM1 Invaginating gapjunction plaquesGJA1 GJC2 TJP1 GJB2 GJB2 AP2M1 CLTCL1 GJD4 GJA1 AP2M1 GJB2CLTA DynaminConnexin 43 connexonGJB1Connexin 32 connexonGJA1 CLTB GJA1 CLTB TJP1 GJB3 GJA10 ADPGJA1Cx26/Cx32MYO6 planar gap junctionplaques associatedwith Dab2GJB1 GJA1 CLTCL1 GJA1 DockedCx43-containingtransport vesiclesSRC-2 CLTCL1 CLTA GJA1 Monomeric connexinproteinConnexin 26 ConnexonCx43:TJP1Connexin 43 hemi-channelCx43 :ZO-1 gapjunctionGJA1 DAB2 DNM2 CLTC TJP1GJA1 SRC-2 ATPCLTA AP2M1 GJB4 TJP1 GJB5 planar gap junctionplaquesSRC-2 DNM1 CLTC DNM2 GJB1 DAB2 CLTC GJA1 Connexin 43 connexonin Golgi transportvesicleGJA1GJB1 CLTB DNM1 MicrotubuleConnexin 26:Connexin32 connexonGJB1


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. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 157858
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Gilleron, J, Segretain, Dominique, Falk, MM

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Ontology Terms

 

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

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AP2M1 ProteinQ96CW1 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
CLTA ProteinP09496 (Uniprot-TrEMBL)
CLTB ProteinP09497 (Uniprot-TrEMBL)
CLTC ProteinQ00610 (Uniprot-TrEMBL)
CLTCL1 ProteinP53675 (Uniprot-TrEMBL)
Connexin 26 ConnexonComplexR-HSA-190641 (Reactome)
Connexin 26:Connexin 32 connexonComplexR-HSA-190632 (Reactome)
Connexin 32 connexonComplexR-HSA-190647 (Reactome)
Connexin 43 hemi-channelComplexR-HSA-158053 (Reactome)
Connexin 43 connexon

in Golgi transport

vesicle
ComplexR-HSA-190583 (Reactome)
Connexin 43 connexonComplexR-HSA-190652 (Reactome)
Connexon 26ComplexR-HSA-112301 (Reactome)
Cx26/Cx32ComplexR-HSA-191076 (Reactome)
Cx26/Cx32ComplexR-HSA-191080 (Reactome)
Cx43 :ZO-1 gap junctionComplexR-HSA-191652 (Reactome)
Cx43:TJP1ComplexR-HSA-191615 (Reactome)
Cx43:ZO-1:c-src gap junctionComplexR-HSA-191653 (Reactome)
DAB2 ProteinP98082 (Uniprot-TrEMBL)
DAB2ProteinP98082 (Uniprot-TrEMBL)
DNM1 ProteinQ05193 (Uniprot-TrEMBL)
DNM2 ProteinP50570 (Uniprot-TrEMBL)
Docked

Cx43-containing

transport vesicles
ComplexR-HSA-194780 (Reactome)
DynaminComplexR-HSA-196042 (Reactome)
F-actin R-HSA-196015 (Reactome)
F-actin R-HSA-196174 (Reactome)
GJA1 ProteinP17302 (Uniprot-TrEMBL)
GJA10 ProteinQ969M2 (Uniprot-TrEMBL)
GJA1ProteinP17302 (Uniprot-TrEMBL)
GJA3 ProteinQ9Y6H8 (Uniprot-TrEMBL)
GJA4 ProteinP35212 (Uniprot-TrEMBL)
GJA5 ProteinP36382 (Uniprot-TrEMBL)
GJA8 ProteinP48165 (Uniprot-TrEMBL)
GJA9 ProteinP57773 (Uniprot-TrEMBL)
GJB1 ProteinP08034 (Uniprot-TrEMBL)
GJB1 mRNARnaENST00000361726.6 (Ensembl)
GJB1ProteinP08034 (Uniprot-TrEMBL)
GJB2 ProteinP29033 (Uniprot-TrEMBL)
GJB2ProteinP29033 (Uniprot-TrEMBL)
GJB3 ProteinO75712 (Uniprot-TrEMBL)
GJB4 ProteinQ9NTQ9 (Uniprot-TrEMBL)
GJB5 ProteinO95377 (Uniprot-TrEMBL)
GJB6 ProteinO95452 (Uniprot-TrEMBL)
GJB7 ProteinQ6PEY0 (Uniprot-TrEMBL)
GJC1 ProteinP36383 (Uniprot-TrEMBL)
GJC2 ProteinQ5T442 (Uniprot-TrEMBL)
GJD2 ProteinQ9UKL4 (Uniprot-TrEMBL)
GJD3 ProteinQ8N144 (Uniprot-TrEMBL)
GJD4 ProteinQ96KN9 (Uniprot-TrEMBL)
Hemi-channelsComplexR-HSA-191070 (Reactome)
Invaginating gap junction plaquesComplexR-HSA-196145 (Reactome)
Junctional channelComplexR-HSA-191068 (Reactome)
MYO6 ProteinQ9UM54 (Uniprot-TrEMBL)
MYO6ProteinQ9UM54 (Uniprot-TrEMBL)
Microtubule protofilament R-HSA-8982424 (Reactome)
MicrotubuleComplexR-HSA-190599 (Reactome)
Monomeric connexin proteinComplexR-HSA-190703 (Reactome)
Planar gap junction

plaques associated with Dab2 and

Dynamin
ComplexR-HSA-196018 (Reactome)
SRC-2 ProteinP12931-2 (Uniprot-TrEMBL)
SRC-2ProteinP12931-2 (Uniprot-TrEMBL)
TJP1 ProteinQ07157 (Uniprot-TrEMBL)
TJP1ProteinQ07157 (Uniprot-TrEMBL)
c-src-associated

Cx43 junctional

channel
ComplexR-HSA-191635 (Reactome)
closed Cx43 junctional channelComplexR-HSA-191637 (Reactome)
connexons in Golgi

transport vesicle docked to

microtubules
ComplexR-HSA-190556 (Reactome)
gap junction plaqueComplexR-HSA-191660 (Reactome)
p-Y265-GJA1 ProteinP17302 (Uniprot-TrEMBL)
phospho-Y265

Cx43:ZO-1 gap

junction
ComplexR-HSA-191645 (Reactome)
planar gap junction

plaques associated

with Dab2
ComplexR-HSA-196033 (Reactome)
planar gap junction plaquesComplexR-HSA-196020 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-191636 (Reactome)
ATPR-HSA-191636 (Reactome)
Connexin 26 ConnexonR-HSA-451056 (Reactome)
Connexin 26:Connexin 32 connexonArrowR-HSA-190687 (Reactome)
Connexin 32 connexonArrowR-HSA-190681 (Reactome)
Connexin 43 hemi-channelArrowR-HSA-190877 (Reactome)
Connexin 43 connexon

in Golgi transport

vesicle
ArrowR-HSA-190782 (Reactome)
Connexin 43 connexon

in Golgi transport

vesicle
R-HSA-190520 (Reactome)
Connexin 43 connexon

in Golgi transport

vesicle
R-HSA-190541 (Reactome)
Connexin 43 connexonArrowR-HSA-190662 (Reactome)
Connexin 43 connexonR-HSA-190782 (Reactome)
Connexon 26ArrowR-HSA-451056 (Reactome)
Cx26/Cx32ArrowR-HSA-190698 (Reactome)
Cx26/Cx32R-HSA-190698 (Reactome)
Cx43 :ZO-1 gap junctionR-HSA-191654 (Reactome)
Cx43:TJP1ArrowR-HSA-190541 (Reactome)
Cx43:ZO-1:c-src gap junctionArrowR-HSA-191654 (Reactome)
Cx43:ZO-1:c-src gap junctionR-HSA-191636 (Reactome)
Cx43:ZO-1:c-src gap junctionmim-catalysisR-HSA-191636 (Reactome)
DAB2R-HSA-196026 (Reactome)
Docked

Cx43-containing

transport vesicles
ArrowR-HSA-191737 (Reactome)
Docked

Cx43-containing

transport vesicles
R-HSA-190877 (Reactome)
DynaminR-HSA-196017 (Reactome)
GJA1ArrowR-HSA-190686 (Reactome)
GJA1ArrowR-HSA-191072 (Reactome)
GJA1R-HSA-190662 (Reactome)
GJA1R-HSA-190686 (Reactome)
GJB1 mRNAR-HSA-190693 (Reactome)
GJB1ArrowR-HSA-190693 (Reactome)
GJB1R-HSA-190681 (Reactome)
GJB1R-HSA-190687 (Reactome)
GJB1mim-catalysisR-HSA-190681 (Reactome)
GJB2ArrowR-HSA-1629787 (Reactome)
GJB2R-HSA-190687 (Reactome)
Hemi-channelsR-HSA-190788 (Reactome)
Invaginating gap junction plaquesArrowR-HSA-190519 (Reactome)
Invaginating gap junction plaquesR-HSA-190829 (Reactome)
Junctional channelArrowR-HSA-190788 (Reactome)
Junctional channelR-HSA-190790 (Reactome)
MYO6R-HSA-190519 (Reactome)
MicrotubuleArrowR-HSA-190877 (Reactome)
MicrotubuleR-HSA-190520 (Reactome)
Monomeric connexin proteinArrowR-HSA-190682 (Reactome)
Planar gap junction

plaques associated with Dab2 and

Dynamin
ArrowR-HSA-196017 (Reactome)
Planar gap junction

plaques associated with Dab2 and

Dynamin
R-HSA-190519 (Reactome)
R-HSA-1629787 (Reactome) Cx26 has also been reported to insert post-translationally into the ER membrane (Zhang et al., 1996; Ahmad et al., 1999 ; Ahmad and Evans, 2002).
R-HSA-190519 (Reactome) GJ plaques, clusters of GJ channels, can be internalized to form large, double-membrane vesicles (aka AGJs). Internalized AGJ vesicles subdivide into smaller vesicles that are subsequently degraded by endo/lysosomal pathways (Piehl et al., 2007).
R-HSA-190520 (Reactome) One mechanism of transport of connexon-containing vesicles involves movement along microtubules (Segretain and Falk, 2004). Such a transport system has been described for similar secretory vesicles (Toomre et al., 1999). Direct microtubule-dependent transport of connexons to GJ-assembly sites has recently been reported as well (Shaw et al., 2007).
R-HSA-190541 (Reactome) Connexin-interacting proteins appear to function in regulating gap junction formation and communication. ZO-1 has been shown to alter the membrane localization of Cx43 and plays a role in regulating Cx43-mediated gap junctional communication in osteoblastic cells (Laing et al. 2005). ZO-1 may function in the delivery of Cx43 from a lipid raft domain to gap junctional plaques, which may be an important regulatory step in gap junction formation.
R-HSA-190662 (Reactome) A study using cultured cells demonstrated connexon oligomerization from Cx43 subunits inside the Trans-Golgi Network after exit from the ER (Musil and Goodenough 1993).
R-HSA-190681 (Reactome) Studies using microsomes have revealed that oligomerization of connexins Cx26, Cx43, and Cx32 can occur after insertion of connexins in the ER membrane (Falk et al. 1997; Ahmad et al. 1999, Ahmad and Evans, 2002).
R-HSA-190682 (Reactome) Connexins (Cxs) are encoded by a large gene family predicted to include at least 20 isoforms in humans. Most mammalian Cx genes consist of two exons. The first consists of untranslated sequence, and the second contains the entire coding sequence. Exceptionally, Cx36 and Cx45 contain 3 exons and 2 introns and the third exon contains the coding sequence (Belluardo et al. 1999 ; Jacob and Beyer 2001). Connexins have been divided in two major subgroups, alpha and beta, according to their amino acid sequence similarity (see Bruzzone et al., 2001; Willecke et al., 2002). Alternative names and additional subgroups have been suggested as well. Cx are synthesized by ribosomes in the endoplasmic reticulum (ER) membrane. All Cx proteins contain four trans-membrane domains (TM1 to TM4), two extracellular loops (E1 and E2) and one cytoplasmic loop. The amino- and carboxyl termini are located in the cytosol (reviewed in Segretain and Falk, 2004). After targeting to the ER, connexins are checked by a quality control system to prevent misfolded forms from progressing through the secretory pathway. Aberrant proteins are removed by endoplasmic-reticulum-associated degradation (ERAD).
R-HSA-190686 (Reactome) Transport of connexins along the secretory pathway (including transit from the Golgi to the TGN where Cx43 is predicted to oligomerize) occurs in vesicular transport containers.
R-HSA-190687 (Reactome) Oligomerization of connexins Cx32 and Cx26 has also been observed in the ER-Golgi-intermediate compartment (ERGIC) (Diez et al. 1999). Heteromeric connexons containing both Cx32 and Cx26 have been observed. For the sake of simplicity, the connexon here is described as containing equal numbers of Cx26 and Cx32 subunits, although the ratio may vary.
R-HSA-190693 (Reactome) Cx proteins are cotranslationally inserted into ER membranes in an SRP (signal recognition particle)-dependent process (Falk et al., 1994).
R-HSA-190698 (Reactome) Transport of connexins along the secretory pathway (including transit from the ER to the ERGIC where Cx32 is predicted to oligomerize) occurs in vesicular transport containers.
R-HSA-190782 (Reactome) Connexon-containing transport vesicles have been shown to emanate from the Golgi and deliver connexons to the plasma membrane (Lauf et al., 2002).
R-HSA-190788 (Reactome) Junctional channels are an assembly of two docked connexons on adjacent cells that permits direct communication of the cytoplasm in the two cells as shown below. Proteins associated with GJs such as catenins (Wu et al., 2003, Shaw et al., 2007) and L-CAM (Musil et al., 1990) might be required for connexon docking. Docking occurs through a tight interaction of the extracellular loops (Unger et al., 1999; Sosinsky and Nicholson, 2005). Intramolecular disulfide bridges between the two extracellular loops (E1 and E2) of connexin polypeptides are important for the correct three-dimensional structure of the extracellular loops (Foote et al., 1998)
R-HSA-190790 (Reactome) Once transported to the plasma membrane, junctional channels aggregate into clusters forming gap junction plaques that may contain a few to many thousands of individual channels and that vary in size from a few square nanometers to many square micrometers (Bruzzone et al. 1996; Falk 2000; Severs et al. 2001). Gap junction plaques are involved in numerous processes including growth and differentiation (Loewenstein and Rose 1992), pathological cell proliferation (Roger et al. 2004; Segretain et al. 2003) and spermatogenesis (Juneja et al. 1999; Plum et al. 2000). The physiological importance of gap junction plaques is underscored by the diverse pathologies associated with connexin gene mutations (De Maio et al. 2002). An arbitrary number (10) of channels is shown as aggregating in this reaction but the actual number may be hundreds to thousands.
R-HSA-190829 (Reactome) Internalized GJ plaques are degraded by lysosomes. Lysosomal degradation appears to be the most common pathway of GJ degradation. (Qin et al., 2003; Grinzberg and Gilula., 1979 ; Berthoud et al., 2004 ; and Leithe et al., 2006).
R-HSA-190877 (Reactome) Hemi-channels appear to play a role in isosmotic cell volume regulation (Quist et al., 2000), in apoptosis regulation (Contreras et al. 2002; John et al. 1999), and in the differentiation of different cell types (Boucher and Bennett 2003). Individual connexons have been observed dispersed around gap junction plaques. This observation suggests that there is a pool of connexons dispersed in the plasma membrane which can migrate to gap junction plaques (Benedetti et al. 2000; Hulser et al. 1997; Lauf et al. 2002; Gaietta et al. 2002).
R-HSA-191072 (Reactome) It has been observed, however, that the oligomerization of Cx43 into connexons does not occur before the Trans-Golgi network (Musil and Goodenough, 1993; Koval, 2006).
R-HSA-191636 (Reactome) c-Src phosphorylates Cx43 on Tyr 265.
R-HSA-191654 (Reactome) c-src has been shown to interact with Cx43 (Giepmans et al., 2001). Models describing v-src mediated Cx43 channel gating propose that the initial interaction between v-src and Cx43 may occur via a SH3 domain interaction (see Lau 2005).
R-HSA-191656 (Reactome) The closure of Cx43 gap junction channels is observed following src-mediated Cx43 phosphorylation.
R-HSA-191737 (Reactome) Docking of Cx43 at the plasma membrane may involve ZO-1 as well as alpha- and beta-catenin (Shaw et al., 2007). The role of ZO-1 in regulating gap junction biology is unclear. Recent results indicate a role for ZO-1 in regulating gap junction plaque size (Hunter et al., 2007).
R-HSA-196017 (Reactome) The GTPase dynamin, which functions in the completion of vesicle budding localizes in Cx43-based GJs and especially invaginating plaques and AGJ vesicles (Piehl et al., 2007).
R-HSA-196026 (Reactome) Dab2 is recruited to Cx43-based GJs possibly through a direct interaction between its N-terminal phosphotyrosine binding (PTB) domain and a putative XPXY internalization motif found in the C-terminal tail of Cx43 as well as a number of other connexin family members (Piehl et al., 2007).The distal portion of Dab2 on its opposite end binds the globular N-terminal domain of clathrin heavy chains (Piehl et al., 2007).
R-HSA-451056 (Reactome) Connexons may also traffic using a microtubule-independent mechanism. A few studies suggest that rough ER membranes can directly transfer connexons to the plasma membrane (Martin et al. 2001; Bloom and Goldstein 1998). Other cytoskeletal components, such as actin filaments, might be involved in the delivery of connexons to gap junction plaques (Thomas et al. 2001; Gilleron et al. 2006).
SRC-2R-HSA-191654 (Reactome)
TJP1R-HSA-190541 (Reactome)
c-src-associated

Cx43 junctional

channel
R-HSA-191656 (Reactome)
closed Cx43 junctional channelArrowR-HSA-191656 (Reactome)
connexons in Golgi

transport vesicle docked to

microtubules
ArrowR-HSA-190520 (Reactome)
connexons in Golgi

transport vesicle docked to

microtubules
R-HSA-191737 (Reactome)
gap junction plaqueArrowR-HSA-190790 (Reactome)
phospho-Y265

Cx43:ZO-1 gap

junction
ArrowR-HSA-191636 (Reactome)
planar gap junction

plaques associated

with Dab2
ArrowR-HSA-196026 (Reactome)
planar gap junction

plaques associated

with Dab2
R-HSA-196017 (Reactome)
planar gap junction plaquesR-HSA-196026 (Reactome)
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