Functional Heterodimerization between the G Protein-Coupled Receptor GPR17 and the Chemokine Receptors 2 and 4: New Evidence.
G protein-coupled receptor (GPCR)
GPR17
chemokine
homology modeling
molecular dynamics
protein-protein interaction
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
23 Dec 2022
23 Dec 2022
Historique:
received:
29
09
2022
revised:
16
12
2022
accepted:
17
12
2022
entrez:
8
1
2023
pubmed:
9
1
2023
medline:
11
1
2023
Statut:
epublish
Résumé
GPR17, a G protein-coupled receptor, is a pivotal regulator of myelination. Its endogenous ligands trigger receptor desensitization and downregulation allowing oligodendrocyte terminal maturation. In addition to its endogenous agonists, GPR17 could be promiscuously activated by pro-inflammatory oxysterols and chemokines released at demyelinating lesions. Herein, the chemokine receptors CXCR2 and CXCR4 were selected to perform both in silico modelling and in vitro experiments to establish their structural and functional interactions with GPR17. The relative propensity of GPR17 and CXCR2 or CXCR4 to form homo- and hetero-dimers was assessed by homology modelling and molecular dynamics (MD) simulations, and co-immunoprecipitation and immunoenzymatic assay. The interaction between chemokine receptors and GPR17 was investigated by determining receptor-mediated modulation of intracellular cyclic adenosine monophosphate (cAMP). Our data show the GPR17 association with CXCR2 or CXCR4 and the negative regulation of these interactions by CXCR agonists or antagonists. Moreover, GPR17 and CXCR2 heterodimers can functionally influence each other. In contrast, CXCR4 can influence GPR17 functionality, but not
Identifiants
pubmed: 36613703
pii: ijms24010261
doi: 10.3390/ijms24010261
pmc: PMC9820414
pii:
doi:
Substances chimiques
Receptors, Chemokine
0
Receptors, G-Protein-Coupled
0
Cyclic AMP
E0399OZS9N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fondazione Italiana Sclerosi Multipla
ID : 2015/R/11
Organisme : Fondazione Italiana Sclerosi Multipla
ID : 222/18/F14
Organisme : Ministry of Education, Universities and Research
ID : "Progetto Eccellenza 2018-2022"
Références
Glia. 2015 Dec;63(12):2327-39
pubmed: 26228571
Science. 2010 Nov 19;330(6007):1066-71
pubmed: 20929726
Sci Rep. 2018 Feb 9;8(1):2730
pubmed: 29426850
Purinergic Signal. 2010 Dec;6(4):373-81
pubmed: 21437008
Am J Cardiol. 1986 Apr 25;57(12):17F-22F
pubmed: 2871741
Int J Mol Sci. 2021 Dec 05;22(23):
pubmed: 34884960
MedComm (2020). 2022 Sep 10;3(4):e159
pubmed: 36105372
J Exp Med. 2013 Aug 26;210(9):1711-28
pubmed: 23897983
Nat Neurosci. 2009 Nov;12(11):1398-406
pubmed: 19838178
J Biol Chem. 2000 Aug 25;275(34):26128-35
pubmed: 10842167
Cell Signal. 2014 Dec;26(12):2614-20
pubmed: 25152366
Proteins. 2012 Aug;80(8):1919-28
pubmed: 22513895
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11685-90
pubmed: 19561298
Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):E3609-18
pubmed: 26100888
Curr Opin Cell Biol. 2014 Apr;27:78-86
pubmed: 24480089
J Biol Chem. 1998 Apr 24;273(17):10095-8
pubmed: 9553055
Br J Pharmacol. 2008 Mar;153 Suppl 1:S379-88
pubmed: 18059321
Int J Mol Sci. 2020 Mar 08;21(5):
pubmed: 32182666
Cell Mol Life Sci. 2009 Apr;66(8):1370-86
pubmed: 19099182
Int J Mol Sci. 2014 Apr 11;15(4):6252-64
pubmed: 24733071
Trends Immunol. 2001 Nov;22(11):612-7
pubmed: 11698222
J Neurosci. 2000 Nov 15;20(22):RC110
pubmed: 11069979
Glia. 2020 Oct;68(10):1957-1967
pubmed: 32086854
Trends Pharmacol Sci. 2018 Apr;39(4):367-386
pubmed: 29395118
Front Chem. 2020 Jan 10;7:910
pubmed: 31998697
Int J Mol Sci. 2020 Mar 31;21(7):
pubmed: 32244295
J Neurosci. 2013 Jun 5;33(23):9752-9768
pubmed: 23739972
Drug Discov Today. 2008 Jul;13(13-14):625-32
pubmed: 18598920
J Biol Chem. 2021 Jan-Jun;296:100139
pubmed: 33268380
Nat Rev Drug Discov. 2002 Oct;1(10):808-20
pubmed: 12360258
EMBO J. 2006 Oct 4;25(19):4615-27
pubmed: 16990797
Nature. 2000 Sep 7;407(6800):94-8
pubmed: 10993080
Nature. 2015 Apr 16;520(7547):317-21
pubmed: 25822790
Nature. 2013 Feb 14;494(7436):185-94
pubmed: 23407534
Front Immunol. 2020 Jan 31;11:94
pubmed: 32076421
J Chem Theory Comput. 2019 Mar 12;15(3):1863-1874
pubmed: 30768902
Science. 2000 Apr 7;288(5463):154-7
pubmed: 10753124
Int J Mol Sci. 2021 Apr 27;22(9):
pubmed: 33925469
J Biol Chem. 1998 Sep 11;273(37):23830-6
pubmed: 9726994
Int J Mol Sci. 2016 Jun 16;17(6):
pubmed: 27322244
Biochem J. 2011 Jan 1;433(1):11-8
pubmed: 21158738
Sci Rep. 2014 Apr 23;4:4749
pubmed: 24756113
Nature. 2008 Mar 6;452(7183):93-7
pubmed: 18297054
Oncogene. 2019 Feb;38(9):1560-1575
pubmed: 30337690
Nature. 1999 Jun 17;399(6737):697-700
pubmed: 10385123
Mol Pharmacol. 2017 May;91(5):518-532
pubmed: 28254957
Int J Mol Sci. 2021 Sep 30;22(19):
pubmed: 34638956
Br J Pharmacol. 2009 Sep;158(1):5-14
pubmed: 19309353
J Biol Chem. 2011 Mar 25;286(12):10593-604
pubmed: 21209081
Immunol Lett. 2012 Jul 30;145(1-2):23-9
pubmed: 22698180
EMBO Rep. 2004 Jan;5(1):30-4
pubmed: 14710183
Acta Neuropathol. 2016 Jul;132(1):23-42
pubmed: 27026411
Neuropharmacology. 2016 May;104:82-93
pubmed: 26453964
Nucleic Acids Res. 2012 Jan;40(Database issue):D370-6
pubmed: 21890895
EMBO Rep. 2020 Apr 3;21(4):e47852
pubmed: 32080959
J Pharmacol Exp Ther. 2011 Aug;338(2):559-67
pubmed: 21531793
Glia. 2011 Dec;59(12):1958-73
pubmed: 21956849
Int J Mol Sci. 2021 Oct 28;22(21):
pubmed: 34769111
Biochem Biophys Res Commun. 2020 Jul 23;528(2):368-375
pubmed: 32085899
PLoS One. 2013 May 07;8(5):e63258
pubmed: 23667595
J Mol Biol. 2002 Jul 12;320(3):597-608
pubmed: 12096912
Nature. 2020 Sep;585(7823):135-140
pubmed: 32610344
BMC Bioinformatics. 2012 Mar 28;13 Suppl 4:S1
pubmed: 22536955
J Biol Chem. 2007 Mar 2;282(9):6906-15
pubmed: 17204468
Neuroscience. 2014 Sep 12;276:29-47
pubmed: 24275321
Cell Signal. 2014 Jun;26(6):1310-25
pubmed: 24613411
Cell Signal. 2016 Jun;28(6):631-42
pubmed: 26971834
PLoS One. 2013 Jun 21;8(6):e65894
pubmed: 23805191
Br J Pharmacol. 2010 Mar;159(5):1092-105
pubmed: 20148890
PLoS One. 2008;3(10):e3579
pubmed: 18974869
J Pharmacol Exp Ther. 2007 Jul;322(1):133-40
pubmed: 17392403
J Immunol. 2005 Jun 1;174(11):6927-33
pubmed: 15905535
Expert Opin Biol Ther. 2008 Nov;8(11):1797-804
pubmed: 18847313
Proteins. 2004 May 1;55(2):351-67
pubmed: 15048827
Cell Death Dis. 2017 Jun 8;8(6):e2871
pubmed: 28594400
Int J Mol Sci. 2022 Feb 04;23(3):
pubmed: 35163700
Int J Mol Sci. 2012;13(3):2636-2649
pubmed: 22489115