Unorthodox localization of P2X7 receptor in subcellular compartments of skeletal system cells.
P2X7 receptor
chondrocytes
immunogold and electron microscopy
intervertebral disc cells
osteoblasts
purinergic signaling
subcellular localization
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2023
2023
Historique:
received:
06
03
2023
accepted:
19
04
2023
medline:
22
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
Identifying the subcellular localization of a protein within a cell is often an essential step in understanding its function. The main objective of this report was to determine the presence of the P2X7 receptor (P2X7R) in healthy human cells of skeletal system, specifically osteoblasts (OBs), chondrocytes (Chs) and intervertebral disc (IVD) cells. This receptor is a member of the ATP-gated ion channel family, known to be a main sensor of extracellular ATP, the prototype of the danger signal released at sites of tissue damage, and a ubiquitous player in inflammation and cancer, including bone and cartilaginous tissues. Despite overwhelming data supporting a role in immune cell responses and tumor growth and progression, a complete picture of the pathophysiological functions of P2X7R, especially when expressed by non-immune cells, is lacking. Here we show that human wild-type P2X7R (P2X7A) was expressed in different samples of human osteoblasts, chondrocytes and intervertebral disc cells. By fluorescence microscopy (LM) and immunogold transmission electron microscopy we localized P2X7R not only in the canonical sites (plasma membrane and cytoplasm), but also in the nucleus of all the 3 cell types, especially IVD cells and OBs. P2X7R mitochondrial immunoreactivity was predominantly detected in OBs and IVD cells, but not in Chs. Evidence of subcellular localization of P2X7R may help to i. understand the participation of P2X7R in as yet unidentified signaling pathways in the joint and bone microenvironment, ii. identify pathologies associated with P2X7R mislocalization and iii. design specific targeted therapies.
Identifiants
pubmed: 37215083
doi: 10.3389/fcell.2023.1180774
pii: 1180774
pmc: PMC10192554
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1180774Informations de copyright
Copyright © 2023 Penolazzi, Notarangelo, Lambertini, Vultaggio-Poma, Tarantini, Di Virgilio and Piva.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Cell Physiol. 2021 Jan;236(1):641-652
pubmed: 32583512
J Biol Chem. 2004 Mar 12;279(11):10808-13
pubmed: 14699115
Function (Oxf). 2021 Jan 28;2(2):zqab005
pubmed: 35330818
Cell. 2009 Aug 21;138(4):628-44
pubmed: 19703392
Cell. 2019 Oct 17;179(3):659-670.e13
pubmed: 31587896
Oncotarget. 2017 Oct 4;8(60):101686-101696
pubmed: 29254196
Methods Mol Biol. 2022;2510:53-63
pubmed: 35776319
BMC Bioinformatics. 2009 Jun 29;10:202
pubmed: 19563654
Nucleus. 2021 Dec;12(1):90-114
pubmed: 34455929
Trends Cell Biol. 2018 May;28(5):392-404
pubmed: 29439897
Aging (Albany NY). 2018 Aug 20;10(8):2001-2015
pubmed: 30130742
Front Pharmacol. 2020 Jan 24;10:1591
pubmed: 32038258
Front Pharmacol. 2021 May 07;12:671809
pubmed: 34025431
Elife. 2016 Jun 09;5:
pubmed: 27278775
FEBS J. 2007 Jun;274(12):3021-33
pubmed: 17498208
J Biol Chem. 2002 Mar 1;277(9):7574-80
pubmed: 11756404
J Mol Endocrinol. 2015 Apr;54(2):R75-88
pubmed: 25591582
Mol Biol Cell. 2005 Jul;16(7):3260-72
pubmed: 15901833
Nature. 2002 Nov 7;420(6911):42
pubmed: 12422208
Front Mol Neurosci. 2019 Aug 07;12:183
pubmed: 31440138
Front Bioeng Biotechnol. 2017 Jun 13;5:35
pubmed: 28660185
Front Genet. 2020 Nov 25;11:607812
pubmed: 33324450
Anal Biochem. 1976 May 7;72:248-54
pubmed: 942051
Science. 2017 May 26;356(6340):
pubmed: 28495876
Traffic. 2015 Oct;16(10):1039-61
pubmed: 26172624
Cells. 2021 Jul 10;10(7):
pubmed: 34359917
Biochem Pharmacol. 2022 Apr;198:114942
pubmed: 35134386
Front Mol Neurosci. 2020 Jul 31;13:124
pubmed: 32848594
Nat Rev Cancer. 2018 Oct;18(10):601-618
pubmed: 30006588
FASEB J. 2010 Sep;24(9):3393-404
pubmed: 20453110
Immunity. 2017 Jul 18;47(1):15-31
pubmed: 28723547
Cell Death Differ. 2023 Feb;30(2):429-441
pubmed: 36450825
Br J Pharmacol. 2018 Nov;175(22):4195-4208
pubmed: 30098011
Purinergic Signal. 2009 Jun;5(2):163-73
pubmed: 19189228
Front Pharmacol. 2020 Jun 04;11:793
pubmed: 32581786
Front Cell Dev Biol. 2021 Feb 11;9:628330
pubmed: 33644066
Bone Res. 2022 Jul 18;10(1):48
pubmed: 35851054
Mol Biol Cell. 2021 Mar 15;32(6):475-491
pubmed: 33476211
Biophys Rev. 2021 Nov 19;13(6):931-941
pubmed: 35047088
Front Cell Neurosci. 2013 Nov 22;7:233
pubmed: 24319412
Purinergic Signal. 2018 Sep;14(3):245-258
pubmed: 29845461
Purinergic Signal. 2011 Mar;7(1):7-19
pubmed: 21484094
Protein Cell. 2017 Jun;8(6):439-445
pubmed: 28271444
Phys Biol. 2020 Oct 13;17(6):061003
pubmed: 32663814
Pharmacol Rev. 2006 Mar;58(1):58-86
pubmed: 16507883
J Cell Physiol. 2022 Feb;237(2):1418-1428
pubmed: 34668208
Science. 2016 Jun 3;352(6290):1221-5
pubmed: 27257257
Biomed Pharmacother. 2020 May;125:110010
pubmed: 32187957
FASEB J. 2009 Mar;23(3):795-805
pubmed: 18971257
Mol Brain. 2021 Jun 3;14(1):86
pubmed: 34082785