A unique mode of keratinocyte death requires intracellular acidification
| Autor: | Takaharu Okada, Yoshiro Suzuki, Sonoko Takahashi, Makoto Tominaga, Masayuki Amagai, Kiminori Toyooka, Azusa Ishida, Hiroshi Kiyonari, Hiroyuki Sasaki, Takaya Abe, Takeshi Matsui, Nanako Kadono-Maekubo, Keiichiro Shiraga, Jafar Sharif, Yuki Furuichi, Atsushi Miyawaki |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Keratinocytes
Programmed cell death Patch-Clamp Techniques Stratum granulosum Mice Transgenic Transient receptor potential channel Mice In vivo medicine Stratum corneum Animals Humans Calcium Signaling Skin Multidisciplinary Corneocyte Cell Death Chemistry Cell Differentiation Biological Sciences Hydrogen-Ion Concentration Cell biology medicine.anatomical_structure Epidermal Cells Commentary Calcium Epidermis Keratinocyte Intracellular |
| Zdroj: | Proc Natl Acad Sci U S A |
| Popis: | 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 Ca(2+)- 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) Ca(2+) 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 Ca(2+) 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. |
| Databáze: | OpenAIRE |
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