title: Phosphorylation controls the interaction of the connexin43 C-terminal domain with tubulin and microtubules.
abstract: Connexins are structurally related transmembrane proteins that assemble to form gap junction channels involved in the mediation of intercellular communication. It has been shown that the intracellular tail of connexin43 (Cx43) interacts with tubulin and microtubules with putative impacts on its own intracellular trafficking, its activity in channel communication, and its interference with specific growth factor signal transduction cascades. We demonstrate here that the microtubule binding of Cx43 is mainly driven by a short region of 26 amino acid residues located within the intracellular tail of Cx43. The nuclear magnetic resonance structural analysis of a peptide (K26D) corresponding to this region shows that this peptide is unstructured when free in solution and adopts a helix conformation upon binding with tubulin. In addition, the resulting K26D-tubulin molecular complex defines a new structural organization that could be shared by other microtubule partners. Interestingly, the K26D-tubulin interaction is prevented by the phosphorylation of K26D at a src kinase specific site. Altogether, the results elucidate the mechanism of the interaction of Cx43 with the microtubule cytoskeleton and propose a pathway for understanding the microtubule-dependent regulation of Cx43 gap junctional communications and the involvement of Cx43 in TGF-β signal transduction.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR829, Université Evry-Val d'Essonne, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Evry 91025, France.
authors.forename: Amal
authors.initials: A
authors.lastname: Saidi Brikci-Nigassa
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Clement
authors.forename: Tap
authors.initials: T
authors.lastname: Ha-Duong
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Adjadj
authors.forename: Latifa
authors.initials: L
authors.lastname: Ziani
authors.forename: David
authors.initials: D
authors.lastname: Pastre
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Curmi
authors.forename: Philippe
authors.initials: P
authors.lastname: Savarin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002450:Cell Communication; D018031:Connexin 43 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012756:Sheep; D014404:Tubulin / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D010446:Peptide Fragments; D014404:Tubulin