2. Academic Validation
  3. Crbn modulates calcium influx by regulating Orai1 during efferocytosis

Crbn modulates calcium influx by regulating Orai1 during efferocytosis

  • Nat Commun. 2020 Oct 30;11(1):5489. doi: 10.1038/s41467-020-19272-0.
Hyunji Moon 1 2,  Chanhyuk Min 1 2,  Gayoung Kim 1,  Deokhwan Kim 1 2,  Kwanhyeong Kim 1 2,  Sang-Ah Lee 1 2,  Byeongjin Moon 1 2,  Susumin Yang 1 2,  Juyeon Lee 1 2,  Seung-Joo Yang 1,  Steve K Cho 1,  Gwangrog Lee 1 2,  Chang Sup Lee 3,  Chul-Seung Park 1,  Daeho Park 4 5 6
Affiliations

Affiliations

  • 1 School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea.
  • 2 Cell Mechanobiology Laboratory, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea.
  • 3 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea.
  • 4 School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea. [email protected].
  • 5 Cell Mechanobiology Laboratory, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea. [email protected].
  • 6 Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 03760, Korea. [email protected].
PMID: 33127885 DOI: 10.1038/s41467-020-19272-0
Abstract

Calcium flux regulating intracellular calcium levels is essential and modulated for efficient efferocytosis. However, the molecular mechanism by which calcium flux is modulated during efferocytosis remains elusive. Here, we report that Orai1, a Crbn substrate, is upregulated via its attenuated interaction with Crbn during efferocytosis, which increases calcium influx into phagocytes and thereby promotes efferocytosis. We found that Crbn deficiency promoted phagocytosis of apoptotic cells, which resulted from facilitated phagocytic cup closure and was nullified by a CRAC Channel Inhibitor. In addition, Orai1 associated with Crbn, resulting in ubiquitination and proteasomal degradation of Orai1 and alteration of SOCE-mediated calcium influx. The association of Orai1 with Crbn was attenuated during efferocytosis, leading to reduced ubiquitination of Orai1 and consequently upregulation of Orai1 and calcium influx. Collectively, our study reveals a regulatory mechanism by which calcium influx is modulated by a Crbn-Orai1 axis to facilitate efferocytosis.

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