マツイ　タケシ   Takeshi Matsui   松井　毅    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2021/04
形態種別	学術論文
査読	査読あり
標題	A unique mode of keratinocyte death requires intracellular acidification
執筆形態	共著
掲載誌名	Proc. Natl. Acad. Sci. USA
掲載区分	国外
出版社・発行元	National Academy of Sciences
著者・共著者	Matsui T, Kadono-Maekubo N, Suzuki Y, Furuichi Y, Shiraga K, Sasaki H, Ishida A, Sonoko Takahashi S, Okada T, Toyooka K, Sharif J, Abe T, Kiyonari H, Tominaga M, Miyawaki A, Amagai M
概要	The stratum corneum (SC), the outermost epidermal layer, consists of nonviable anuclear keratinocytes, called corneocytes, which function as a protective barrier. The exact modes of cell death executed by keratinocytes of the upper stratum granulosum (SG1 cells) remain largely unknown. Here, using intravital imaging combined with intracellular Ca2+- and pH-responsive fluorescent probes, we aimed to dissect the SG1 death process in vivo. We found that SG1 cell death was preceded by prolonged ( 60 min) Ca2+ elevation and rapid induction of intracellular acidification. Once such intracellular ionic changes were initiated, they became sustained, irreversibly committing the SG1 cells to corneocyte conversion. Time-lapse imaging of isolated murine SG1 cells revealed that intracellular acidification was essential for the degradation of keratohyalin granules and nuclear DNA, phenomena specific to SC corneocyte formation. Furthermore, intravital imaging showed that the number of SG1 cells exhibiting Ca2+ elevation and the timing of intracellular acidification were both tightly regulated by the transient receptor potential cation channel V3. The functional activity of this protein was confirmed in isolated SG1 cells using whole-cell patch-clamp analysis. These findings provide a theoretical framework for improved understanding of the unique molecular mechanisms underlying keratinocyte-specific death mode, namely corneoptosis.
外部リンクURL	https://www.pnas.org/content/118/17/e2020722118