title: Dynamin 2 interacts with connexin 26 to regulate its degradation and function in gap junction formation.
abstract: Connexin 26 (Cx26), a protein involved in gap junctional intercellular communication, has an essential function during organ and tissue development. Its deregulation, in part due to inherent mutations, is associated with pathological conditions including congenital deafness. Regulation of Cx26 protein level is critical for its function but the molecular mechanisms involved are partially understood. This study identifies dynamin 2 (Dyn2) as a Cx26 interactor in yeast and mammalian cells. Deletion studies revealed that Cx26-Dyn2 interaction involves the C-terminus of Cx26 and the GTPase effector domain of Dyn2, which is of particular importance for the regulation of the endocytic pathway. Dyn2 inhibition using siRNA or dynasore resulted in reduced Cx26 degradation at the plasma membrane and this was associated with change in gap junctional intercellular communication (GJIC). Furthermore, we demonstrate that Dyn2 regulates Cx26 endocytosis and ubiquitination. These results establish Dyn2 as a Cx26 partner in the regulation of GJIC.
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China. Electronic address: dzhxiao@163.com.
authors.forename: Dingzhang
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Shaoxian
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Lady Davis Institute and Segal Cancer Center of the Sir Mortimer B. Davis Jewish General Hospital, Department of Medicine and Oncology, McGill University, Montreal, QC, Canada H3T 1E2.
authors.forename: Krikor
authors.initials: K
authors.lastname: Bijian
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Laird
authors.affiliation: Lady Davis Institute and Segal Cancer Center of the Sir Mortimer B. Davis Jewish General Hospital, Department of Medicine and Oncology, McGill University, Montreal, QC, Canada H3T 1E2. Electronic address: moulay.alaoui-jamali@mcgill.ca.
authors.forename: Moulay A
authors.initials: MA
authors.lastname: Alaoui-Jamali
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D017629:Gap Junctions / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D011485:Protein Binding; D059748:Proteolysis; D034622:RNA Interference; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D034285:Dynamin II
keywords: Connexin 26; Dynamin 2; Gap junction; Turnover