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Crbn modulates calcium influx by regulating Orai1 during efferocytosis

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 inter...

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Autores principales: Moon, Hyunji, Min, Chanhyuk, Kim, Gayoung, Kim, Deokhwan, Kim, Kwanhyeong, Lee, Sang-Ah, Moon, Byeongjin, Yang, Susumin, Lee, Juyeon, Yang, Seung-Joo, Cho, Steve K., Lee, Gwangrog, Lee, Chang Sup, Park, Chul-Seung, Park, Daeho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603501/
https://www.ncbi.nlm.nih.gov/pubmed/33127885
http://dx.doi.org/10.1038/s41467-020-19272-0
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author Moon, Hyunji
Min, Chanhyuk
Kim, Gayoung
Kim, Deokhwan
Kim, Kwanhyeong
Lee, Sang-Ah
Moon, Byeongjin
Yang, Susumin
Lee, Juyeon
Yang, Seung-Joo
Cho, Steve K.
Lee, Gwangrog
Lee, Chang Sup
Park, Chul-Seung
Park, Daeho
author_facet Moon, Hyunji
Min, Chanhyuk
Kim, Gayoung
Kim, Deokhwan
Kim, Kwanhyeong
Lee, Sang-Ah
Moon, Byeongjin
Yang, Susumin
Lee, Juyeon
Yang, Seung-Joo
Cho, Steve K.
Lee, Gwangrog
Lee, Chang Sup
Park, Chul-Seung
Park, Daeho
author_sort Moon, Hyunji
collection PubMed
description 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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spelling pubmed-76035012020-11-10 Crbn modulates calcium influx by regulating Orai1 during efferocytosis Moon, Hyunji Min, Chanhyuk Kim, Gayoung Kim, Deokhwan Kim, Kwanhyeong Lee, Sang-Ah Moon, Byeongjin Yang, Susumin Lee, Juyeon Yang, Seung-Joo Cho, Steve K. Lee, Gwangrog Lee, Chang Sup Park, Chul-Seung Park, Daeho Nat Commun Article 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. Nature Publishing Group UK 2020-10-30 /pmc/articles/PMC7603501/ /pubmed/33127885 http://dx.doi.org/10.1038/s41467-020-19272-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Moon, Hyunji
Min, Chanhyuk
Kim, Gayoung
Kim, Deokhwan
Kim, Kwanhyeong
Lee, Sang-Ah
Moon, Byeongjin
Yang, Susumin
Lee, Juyeon
Yang, Seung-Joo
Cho, Steve K.
Lee, Gwangrog
Lee, Chang Sup
Park, Chul-Seung
Park, Daeho
Crbn modulates calcium influx by regulating Orai1 during efferocytosis
title Crbn modulates calcium influx by regulating Orai1 during efferocytosis
title_full Crbn modulates calcium influx by regulating Orai1 during efferocytosis
title_fullStr Crbn modulates calcium influx by regulating Orai1 during efferocytosis
title_full_unstemmed Crbn modulates calcium influx by regulating Orai1 during efferocytosis
title_short Crbn modulates calcium influx by regulating Orai1 during efferocytosis
title_sort crbn modulates calcium influx by regulating orai1 during efferocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603501/
https://www.ncbi.nlm.nih.gov/pubmed/33127885
http://dx.doi.org/10.1038/s41467-020-19272-0
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