Apoptotic cells trigger calcium entry in phagocytes by inducing the orai1-stim1 association

Deokhwan Kim, Hyunji Moon, Hyeokjin Cho, Chanhyuk Min, Byeongjin Moon, Susumin Yang, Juyeon Lee, Sang Ah Lee, Hyunjin Park, Dae Hee Lee, Dongtak Jeong, Gwangrog Lee, Daeho Park

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Swift and continuous phagocytosis of apoptotic cells can be achieved by modulation of calcium flux in phagocytes. However, the molecular mechanism by which apoptotic cells modulate calcium flux in phagocytes is incompletely understood. Here, using biophysical, biochemical, pharmaceutical, and genetic approaches, we show that apoptotic cells induced the Orai1-STIM1 interaction, leading to store-operated calcium entry (SOCE) in phagocytes through the Mertk-phospholipase C (PLC) γ1-inositol 1,4,5-triphosphate receptor (IP3R) axis. Apoptotic cells induced calcium release from the endoplasmic reticulum, which led to the Orai1-STIM1 association and, consequently, SOCE in phagocytes. This association was attenuated by masking phosphatidylserine. In addition, the depletion of Mertk, which indirectly senses phosphatidylserine on apoptotic cells, reduced the phosphorylation levels of PLCγ1 and IP3R, resulting in attenuation of the Orai1-STIM1 interaction and inefficient SOCE upon apoptotic cell stimulation. Taken together, our observations uncover the mechanism of how phagocytes engulfing apoptotic cells elevate the calcium level.

Original languageEnglish
Article number2702
JournalCells
Volume10
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

Keywords

  • Calcium flux
  • Efferocytosis
  • Interaction
  • Mertk
  • Orai1
  • SOCE
  • STIM1

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