title: Cdo Regulates Surface Expression of Kir2.1 K+ Channel in Myoblast Differentiation.
abstract: A potassium channel Kir2.1-associated membrane hyperpolarization is required for myogenic differentiation. However the molecular regulatory mechanisms modulating Kir2.1 channel activities in early stage of myogenesis are largely unknown. A cell surface protein, Cdo functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that Cdo forms a complex with Kir2.1 during myogenic differentiation, and is required for the channel activity by enhancing the surface expression of Kir2.1 in the early stage of differentiation. The expression of a constitutively active form of the upstream kinase for p38MAPK, MKK6(EE) can restore Kir2.1 activities in Cdo-depleted C2C12 cells, while the treatment with a p38MAPK inhibitor, SB203580 exhibits a similar effect of Cdo depletion on Kir2.1 surface expression. Furthermore, Cdo-/- primary myoblasts, which display a defective differentiation program, exhibit a defective Kir2.1 activity. Taken together, our results suggest that a promyogenic Cdo signaling is critical for Kir2.1 activities in the induction of myogenic differentiation.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Leem
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Hyeon-Ju
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Jewoo
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Anatomy, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: KyeongJin
authors.initials: K
authors.lastname: Kang
authors.affiliation: Research Center for Cell Fate Control, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D007093:Imidazoles; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482567:Map2k6 protein, mouse; C093642:SB 203580