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Crbn modulates calcium influx by regulating Orai1 during efferocytosis

Hyunji Moon1,2, Chanhyuk Min1,2, Gayoung Kim1

  • 1School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea.

Nature Communications
|October 31, 2020
PubMed

Insights

Researchers discovered that Orai1, a protein, increases during efferocytosis (cell clearance) by interacting less with Crbn. This boosts calcium influx, enhancing efferocytosis and promoting the removal of apoptotic cells.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Intracellular calcium levels, regulated by calcium flux, are crucial for efficient efferocytosis.
  • The precise molecular mechanisms modulating calcium flux during efferocytosis are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism regulating calcium flux during efferocytosis.
  • To investigate the role of Orai1 and Crbn in modulating calcium influx and efferocytosis.

Main Methods:

  • Investigated the interaction between Orai1 and Crbn.
  • Analyzed Orai1 ubiquitination and proteasomal degradation.
  • Assessed the impact of Crbn deficiency and CRAC channel inhibition on phagocytosis.

Main Results:

  • Orai1, a Crbn substrate, is upregulated during efferocytosis due to reduced interaction with Crbn.
  • This upregulation increases calcium influx into phagocytes, enhancing efferocytosis and phagocytic cup closure.
  • Crbn deficiency promotes efferocytosis, an effect reversed by CRAC channel inhibition.

Conclusions:

  • A novel regulatory mechanism involving a Crbn-Orai1 axis controlling calcium influx during efferocytosis has been identified.
  • This axis modulates calcium flux, thereby facilitating the efficient clearance of apoptotic cells.

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