Crbn modulates calcium influx by regulating Orai1 during efferocytosis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 10 2020
30 10 2020
Historique:
received:
31
10
2019
accepted:
07
10
2020
entrez:
31
10
2020
pubmed:
1
11
2020
medline:
18
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33127885
doi: 10.1038/s41467-020-19272-0
pii: 10.1038/s41467-020-19272-0
pmc: PMC7603501
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Calcium Channels
0
Crbn protein, mouse
0
ORAI1 Protein
0
Orai1 protein, mouse
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5489Références
Blood. 1995 Apr 15;85(8):2194-201
pubmed: 7718891
Diabetes. 2013 Jun;62(6):1855-64
pubmed: 23349485
Arch Biochem Biophys. 1992 Oct;298(1):187-91
pubmed: 1388011
Nat Commun. 2019 Apr 29;10(1):1971
pubmed: 31036819
Nature. 2006 May 11;441(7090):179-85
pubmed: 16582901
Adv Exp Med Biol. 2016;898:25-46
pubmed: 27161223
Curr Biol. 2007 May 1;17(9):794-800
pubmed: 17442569
Nature. 2011 Aug 21;477(7363):220-4
pubmed: 21857682
Biochim Biophys Acta. 2014 Nov;1843(11):2438-47
pubmed: 25063526
Science. 1985 Nov 8;230(4726):663-6
pubmed: 4048951
Nature. 2002 May 9;417(6885):182-7
pubmed: 12000961
Nature. 2014 Aug 7;512(7512):49-53
pubmed: 25043012
Nature. 2001 May 10;411(6834):207-11
pubmed: 11346799
FASEB J. 2011 Dec;25(12):4358-68
pubmed: 21885655
Biochim Biophys Acta. 2011 Mar;1813(3):448-55
pubmed: 21232561
Neurology. 2004 Nov 23;63(10):1927-31
pubmed: 15557513
J Cell Sci. 2012 Sep 15;125(Pt 18):4354-61
pubmed: 22641696
Annu Rev Cell Dev Biol. 2017 Oct 6;33:127-144
pubmed: 28613937
Cell Death Differ. 2009 Oct;16(10):1323-31
pubmed: 19461656
Cell. 2008 Oct 31;135(3):524-34
pubmed: 18984163
Nat Commun. 2017 Mar 15;8:14714
pubmed: 28294127
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8771-6
pubmed: 27439875
PLoS One. 2015 May 28;10(5):e0127885
pubmed: 26020972
Cell. 2017 Oct 5;171(2):331-345.e22
pubmed: 28942921
Mol Cell. 2016 Mar 17;61(6):809-20
pubmed: 26990986
Nat Commun. 2014 May 21;5:3924
pubmed: 24845235
J Physiol. 2008 Nov 15;586(22):5383-401
pubmed: 18832420
Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9198-203
pubmed: 18591655
J Leukoc Biol. 2010 Jul;88(1):57-68
pubmed: 20400677
Physiol Rev. 2015 Oct;95(4):1383-436
pubmed: 26400989
Nature. 2016 Jun 22;535(7611):252-7
pubmed: 27338790
Nature. 2006 Oct 5;443(7111):590-3
pubmed: 16964240
J Biol Chem. 2013 Sep 6;288(36):26013-26
pubmed: 23897815
Cell Death Differ. 2016 Jun;23(6):915-26
pubmed: 26990661
J Neurochem. 2005 Sep;94(5):1212-24
pubmed: 16045448
Curr Biol. 2005 Jul 12;15(13):1235-41
pubmed: 16005298
Cold Spring Harb Perspect Biol. 2013 Jan 01;5(1):a008748
pubmed: 23284042
Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62
pubmed: 16751269
Sci Signal. 2015 Jul 28;8(387):ra74
pubmed: 26221052
Nature. 2015 Jul 9;523(7559):183-188
pubmed: 26131937
PLoS One. 2017 Jul 3;12(7):e0180213
pubmed: 28671983
Cell Death Differ. 2019 Sep;26(9):1646-1655
pubmed: 30451988
Nature. 2007 Nov 15;450(7168):435-9
pubmed: 17960135
Nature. 2007 Nov 15;450(7168):430-4
pubmed: 17960134
Immunity. 2019 May 21;50(5):1149-1162
pubmed: 31117011
Adv Biol Regul. 2018 May;68:88-96
pubmed: 29217255
Immunity. 2007 Dec;27(6):941-51
pubmed: 18083575
FEBS Lett. 2009 Feb 18;583(4):633-7
pubmed: 19166841
J Biol Chem. 1997 Nov 21;272(47):29411-4
pubmed: 9367994
Nat Med. 2009 Nov;15(11):1266-72
pubmed: 19838202
J Biol Chem. 2007 Jun 1;282(22):16232-43
pubmed: 17293345
Science. 2014 Jan 17;343(6168):305-9
pubmed: 24292623
Science. 2010 Mar 12;327(5971):1345-50
pubmed: 20223979
J Physiol. 2012 Jan 15;590(2):241-57
pubmed: 22041188