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DOI10.1073/pnas.2020722118
A unique mode of keratinocyte death requires intracellular acidification
Matsui T.; Kadono-Maekubo N.; Suzuki Y.; Furuichi Y.; Shiraga K.; Sasaki H.; Ishida A.; Takahashi S.; Okada T.; Toyooka K.; Sharif J.; Abe T.; Kiyonari H.; Tominaga M.; Miyawaki A.; Amagai M.
发表日期2021
ISSN00278424
卷号118期号:17
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Acidification; Cell death; Corneoptosis; Cornification; Keratinocytes
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/179736
作者单位Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan; Department of Dermatology, Keio University School of Medicine, Tokyo, 160-8582, Japan; Division of Cell Signaling, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, 444-8787, Japan; Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, 230-0045, Japan; Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science, Yokohama, 230-0045, Japan; Laboratory for Developmental Biology, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, 650-0047, Japan; Laboratory for Cell Function Dynamics, RIKEN Center for Brain Science, Wako, 351-0198, Japan
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Matsui T.,Kadono-Maekubo N.,Suzuki Y.,et al. A unique mode of keratinocyte death requires intracellular acidification[J],2021,118(17).
APA Matsui T..,Kadono-Maekubo N..,Suzuki Y..,Furuichi Y..,Shiraga K..,...&Amagai M..(2021).A unique mode of keratinocyte death requires intracellular acidification.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA Matsui T.,et al."A unique mode of keratinocyte death requires intracellular acidification".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).
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