title: The large GTPase dynamin2: a new player in connexin 43 gap junction endocytosis, recycling and degradation.
abstract: Connexins (Cx) are key regulators of cell proliferation, differentiation and apoptosis. Cx trafficking and endocytosis need interactions with a large number of signaling and scaffolding proteins. We demonstrate herein that Cx43-GFP gap junction plaque endocytosis was blocked in cells transfected by the dominant-negative form of dynamin2 (Dyn2K44A) and by dynasore, an inhibitor of dynamin GTPase activity, which reduced the association between dynamin2 and Cx43. Our data also reveal that recruitment of the GTPase at the plasma membrane and its activation by c-Src are key events for Cx43 internalization. In addition they show that dynamin2 participated in internalization and degradation of the gap junction plaque but also in recycling of Cx43 to the plasma membrane through respectively Rab5/Rab7 and Rab11 pathways. These results demonstrate for the first time that dynamin2 is a new Cx partner and report an innovating mechanistic model by which dynamin2 may control Cx43 gap junction plaque invagination, endocytosis, recycling and degradation. These processes are magnified in response to carcinogen exposure underlining their potential importance during carcinogenesis.
authors.affiliation: INSERM U 895, Bâtiment Universitaire Archimed, 151 route Saint-Antoine de Ginestière, BP 2 3194, 06204 Nice, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gilleron
authors.forename: Diane
authors.initials: D
authors.lastname: Carette
authors.forename: Céline
authors.initials: C
authors.lastname: Fiorini
authors.forename: Jim
authors.initials: J
authors.lastname: Dompierre
authors.forename: Eric
authors.initials: E
authors.lastname: Macia
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Denizot
authors.forename: Dominique
authors.initials: D
authors.lastname: Segretain
authors.forename: Georges
authors.initials: G
authors.lastname: Pointis
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D034285:Dynamin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004705:Endocytosis; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D008297:Male; D012708:Sertoli Cells / Q000378:metabolism; D014162:Transfection
chemical_list: D018031:Connexin 43; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D034285:Dynamin II