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Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage.
Sakamaki, Kazuhiro; Ishii, Takahiro M; Sakata, Toshiya; Takemoto, Kiwamu; Takagi, Chiyo; Takeuchi, Ayako; Morishita, Ryo; Takahashi, Hirotaka; Nozawa, Akira; Shinoda, Hajime; Chiba, Kumiko; Sugimoto, Haruyo; Saito, Akiko; Tamate, Shuhei; Satou, Yutaka; Jung, Sang-Kee; Matsuoka, Satoshi; Koyamada, Koji; Sawasaki, Tatsuya; Nagai, Takeharu; Ueno, Naoto.
Afiliação
  • Sakamaki K; Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan. Electronic address: sakamaki.kazuhiro.7u@kyoto-u.ac.jp.
  • Ishii TM; Department of Physiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
  • Sakata T; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
  • Takemoto K; Research Institute for Electronic Science, Hokkaido University, Sapporo 001-0020, Japan.
  • Takagi C; Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
  • Takeuchi A; Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
  • Morishita R; CellFree Sciences Co., Ltd., Yokohama 230-0046, Japan.
  • Takahashi H; Proteo-Science Center, Ehime University, Matsuyama 790-8577, Japan.
  • Nozawa A; Proteo-Science Center, Ehime University, Matsuyama 790-8577, Japan.
  • Shinoda H; The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
  • Chiba K; Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
  • Sugimoto H; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
  • Saito A; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
  • Tamate S; Department of Electronic Science and Engineering, Graduate School of Engineering, Kyoto University, Kyoto 615-8530, Japan.
  • Satou Y; Department of Zoology, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
  • Jung SK; SCOTS, Tensei Suisan Co., Ltd., Karatsu 847-0193, Japan.
  • Matsuoka S; Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
  • Koyamada K; Center for Promotion of Excellence in Higher Education, Kyoto University, Kyoto 606-8501, Japan.
  • Sawasaki T; Proteo-Science Center, Ehime University, Matsuyama 790-8577, Japan.
  • Nagai T; Research Institute for Electronic Science, Hokkaido University, Sapporo 001-0020, Japan; The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
  • Ueno N; Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Biochim Biophys Acta ; 1863(11): 2766-2783, 2016 11.
Article em En | MEDLINE | ID: mdl-27566292
Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the physiological role of CASP8 is not fully understood. Here, we identified a two-pore domain potassium channel, tandem-pore domain halothane-inhibited K+ channel 1 (THIK-1), as a novel CASP8 substrate. The intracellular region of THIK-1 was cleaved by CASP8 in apoptotic cells. Overexpression of THIK-1, but not its mutant lacking the CASP8-target sequence in the intracellular portion, accelerated cell shrinkage in response to apoptotic stimuli. In contrast, knockdown of endogenous THIK-1 by RNA interference resulted in delayed shrinkage and potassium efflux. Furthermore, a truncated THIK-1 mutant lacking the intracellular region, which mimics the form cleaved by CASP8, led to a decrease of cell volume of cultured cells without apoptotic stimulation and excessively promoted irregular development of Xenopus embryos. Taken together, these results indicate that THIK-1 is involved in the acceleration of cell shrinkage. Thus, we have demonstrated a novel physiological role of CASP8: creating a cascade that advances the cell to the next stage in the apoptotic process.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canais de Potássio de Domínios Poros em Tandem / Tamanho Celular / Caspase 8 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canais de Potássio de Domínios Poros em Tandem / Tamanho Celular / Caspase 8 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article