2016年11月
Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
- 巻
- 1863
- 号
- 11
- 開始ページ
- 2766
- 終了ページ
- 2783
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bbamcr.2016.08.010
- 出版者・発行元
- ELSEVIER SCIENCE BV
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. (C) 2016 Elsevier B.V. All rights reserved.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.bbamcr.2016.08.010
- ISSN : 0167-4889
- eISSN : 0006-3002
- PubMed ID : 27566292
- Web of Science ID : WOS:000385329900021