title: KCNK10, a tandem pore domain potassium channel, is a regulator of mitotic clonal expansion during the early stage of adipocyte differentiation.
abstract: KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. We also demonstrated that KCNK10 functions as a positive regulator of mitotic clonal expansion (MCE), a necessary process for terminal differentiation. The reduction of kcnk10 expression repressed the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPδ as well as the phosphorylation level of Akt during the early phase of adipogenesis. In addition, knockdown of kcnk10 expression suppressed insulin-induced Akt phosphorylation. These results indicate that KCNK10 contributes to the regulation of MCE through the control of C/EBPβ and C/EBPδ expression and insulin signaling.
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. prmakoto@phar.nagoya-cu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishizuka
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. p052759@phar.nagoya-cu.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. p112711@phar.nagoya-cu.ac.jp.
authors.forename: Mami
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. osada@phar.nagoya-cu.ac.jp.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Osada
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. imagawa@phar.nagoya-cu.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Imagawa
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D060965:Clonal Evolution / Q000235:genetics*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D010766:Phosphorylation; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D007328:Insulin; C503445:Kcnk10 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; D051743:CCAAT-Enhancer-Binding Protein-delta