RGD Reference Report - Connexin43 Forms Supramolecular Complexes through Non-Overlapping Binding Sites for Drebrin, Tubulin, and ZO-1. - Rat Genome Database

RGD Reference Report - Connexin43 Forms Supramolecular Complexes through Non-Overlapping Binding Sites for Drebrin, Tubulin, and ZO-1. - Rat Genome Database

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Connexin43 Forms Supramolecular Complexes through Non-Overlapping Binding Sites for Drebrin, Tubulin, and ZO-1.
Authors:	Ambrosi, Cinzia Ren, Cynthia Spagnol, Gaelle Cavin, Gabriel Cone, Angela Grintsevich, Elena E Sosinsky, Gina E Sorgen, Paul L
Citation:	Ambrosi C, etal., PLoS One. 2016 Jun 9;11(6):e0157073. doi: 10.1371/journal.pone.0157073. eCollection 2016.
RGD ID:	14397581
Pubmed:	PMID:27280719 (View Abstract at PubMed)
PMCID:	PMC4900556 (View Article at PubMed Central)
DOI:	DOI:10.1371/journal.pone.0157073 (Journal Full-text)
Gap junctions are membrane specialization domains identified in most tissue types where cells abut each other. The connexin channels found in these membrane domains are conduits for direct cell-to-cell transfer of ions and molecules. Connexin43 (Cx43) is the most ubiquitous connexin, with critical roles in heart, skin, and brain. Several studies described the interaction between Cx43 and the cytoskeleton involving the actin binding proteins Zonula occludens (ZO-1) and drebrin, as well as with tubulin. However, a direct interaction has not been identified between drebrin and Cx43. In this study, co-IP and NMR experiments were used to demonstrate that the Cx43-CT directly interacts with the highly conserved N-terminus region of drebrin. Three Cx43-CT areas were found to be involved in drebrin binding, with residues 264-275 being critical for the interaction. Mimicking Src phosphorylation within this region (Y265) significantly disrupted the interaction between the Cx43-CT and drebrin. Immunofluorescence showed colocalization of Cx43, drebrin, and F-actin in astrocytes and Vero cells membrane, indicating that Cx43 forms a submembrane protein complex with cytoskeletal and scaffolding proteins. The co-IP data suggest that Cx43 indirectly interacts with F-actin through drebrin. Along with the known interaction of the Cx43-CT with ZO-1 and tubulin, the data presented here for drebrin indicate non-overlapping and separated binding sites for all three proteins for which simultaneous binding could be important in regulating cytoskeleton rearrangements, especially for neuronal migration during brain development.

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Dbn1	Rat	protein binding	enables	IPI	UniProtKB:P08050	PMID:27280719	UniProt
Gja1	Rat	protein binding	enables	IPI	UniProtKB:Q07266	PMID:27280719	UniProt

Genes (Rattus norvegicus)


Dbn1 (drebrin 1)	Gja1 (gap junction protein, alpha 1)