دورية أكاديمية
أعرض في EDS

AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration.

التفاصيل البيبلوغرافية
العنوان: AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration.
المؤلفون: Thotamune W; Department of Chemistry, Saint Louis University, Saint Louis, MO 63103, USA.; Institute for Drug and Biotherapeutic Innovation, Saint Louis University, Saint Louis, MO 63103, USA., Ubeysinghe S; Department of Chemistry, Saint Louis University, Saint Louis, MO 63103, USA.; Institute for Drug and Biotherapeutic Innovation, Saint Louis University, Saint Louis, MO 63103, USA., Rajarathna C; Department of Chemistry, Saint Louis University, Saint Louis, MO 63103, USA.; Institute for Drug and Biotherapeutic Innovation, Saint Louis University, Saint Louis, MO 63103, USA., Kankanamge D; Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine; St. Louis, MO 63110 USA., Olupothage K; Department of Chemistry and Biochemistry, The University of Toledo, Toledo, OH 43606, USA., Chandu A; Department of Chemistry, Saint Louis University, Saint Louis, MO 63103, USA., Copits BA; Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine; St. Louis, MO 63110 USA., Karunarathne A; Department of Chemistry, Saint Louis University, Saint Louis, MO 63103, USA.; Institute for Drug and Biotherapeutic Innovation, Saint Louis University, Saint Louis, MO 63103, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 05. Date of Electronic Publication: 2024 Jun 05.
نوع المنشور: Journal Article; Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: G protein-coupled receptors (GPCRs) are efficient Guanine nucleotide exchange factors (GEFs) and exchange GDP to GTP on the Gα subunit of G protein heterotrimers in response to various extracellular stimuli, including neurotransmitters and light. GPCRs primarily broadcast signals through activated G proteins, GαGTP, and free Gβγ, and are major disease drivers. Evidence shows that the ambient low threshold signaling required for cells is likely supplemented by signaling regulators such as non-GPCR GEFs and Guanine nucleotide Dissociation Inhibitors (GDIs). Activators of G protein Signaling 3 (AGS3) are recognized as a GDI involved in multiple health and disease-related processes. Nevertheless, understanding of AGS3 is limited, and no significant information is available on its structure-function relationship or signaling regulation in living cells. Here, we employed in silico structure-guided engineering of a novel optogenetic GDI, based on the AGS3's G protein regulatory (GPR) motif, to understand its GDI activity and induce standalone Gβγ signaling in living cells on optical command. Our results demonstrate that plasma membrane recruitment of OptoGDI efficiently releases Gβγ, and its subcellular targeting generated localized PIP3 and triggered macrophage migration. Therefore, we propose OptoGDI as a powerful tool for optically dissecting GDI-mediated signaling pathways and triggering GPCR-independent Gβγ signaling in cells and in vivo .
Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest concerning the contents of this article.
References: FEBS Lett. 1996 Jul 22;390(2):217-20. (PMID: 8706863)
J Biol Chem. 2000 Dec 29;275(52):40981-5. (PMID: 11024022)
Eur J Biochem. 1992 Jun 15;206(3):821-31. (PMID: 1606965)
J Biol Chem. 2002 Dec 27;277(52):50223-5. (PMID: 12426323)
J Biol Chem. 2000 Dec 22;275(51):39846-54. (PMID: 10995757)
Cell Mol Life Sci. 2008 Jul;65(14):2191-214. (PMID: 18488142)
J Biol Chem. 1995 Dec 8;270(49):29059-62. (PMID: 7493925)
J Biol Chem. 2003 Sep 12;278(37):34747-50. (PMID: 12881533)
Cells. 2021 Nov 24;10(12):. (PMID: 34943797)
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8746-51. (PMID: 15937104)
Signal Transduct Target Ther. 2021 Jan 8;6(1):7. (PMID: 33414387)
Biochem Biophys Res Commun. 2012 May 11;421(3):605-11. (PMID: 22538369)
Mol Psychiatry. 2023 Feb;28(2):588-600. (PMID: 36357671)
Cancers (Basel). 2020 Apr 23;12(4):. (PMID: 32340161)
Mol Biol Cell. 2021 Aug 1;32(16):1446-1458. (PMID: 34106735)
Pharmacol Ther. 2022 Mar;231:107977. (PMID: 34480967)
Cell Syst. 2021 Apr 21;12(4):324-337.e5. (PMID: 33667409)
J Biol Chem. 2022 Dec;298(12):102618. (PMID: 36272647)
J Cell Sci. 2008 Mar 1;121(Pt 5):551-9. (PMID: 18287584)
PLoS Comput Biol. 2006 Feb;2(2):e13. (PMID: 16485037)
Neurosignals. 2009;17(1):55-70. (PMID: 19212140)
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14364-9. (PMID: 11121039)
Cell Mol Life Sci. 2005 Mar;62(5):551-77. (PMID: 15747061)
J Biol Chem. 2001 Jan 12;276(2):1585-93. (PMID: 11042168)
Int J Mol Sci. 2018 Jun 27;19(7):. (PMID: 29954076)
Plant Signal Behav. 2009 Oct;4(10):942-7. (PMID: 19826234)
Cancer Res. 2009 Jul 15;69(14):5743-51. (PMID: 19549919)
Cell Signal. 2019 Jun;58:34-43. (PMID: 30849518)
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18103-8. (PMID: 17991770)
Science. 1992 Aug 28;257(5074):1264-7. (PMID: 1325672)
Mol Biol Cell. 2016 May 1;27(9):1442-50. (PMID: 26941336)
Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1565-74. (PMID: 23479634)
J Neurosci Methods. 2011 Jul 15;199(1):1-9. (PMID: 21497167)
Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844)
Elife. 2020 Sep 16;9:. (PMID: 32936073)
Trends Pharmacol Sci. 2005 Sep;26(9):470-6. (PMID: 16084602)
Anal Chem. 2016 Dec 6;88(23):11450-11459. (PMID: 27778511)
J Biol Chem. 2017 Oct 20;292(42):17482-17495. (PMID: 28864771)
Nat Chem Biol. 2020 Aug;16(8):841-849. (PMID: 32367019)
Rev Physiol Biochem Pharmacol. 2005;155:57-80. (PMID: 16041530)
ACS Synth Biol. 2024 Jan 19;13(1):242-258. (PMID: 38092428)
Int J Mol Sci. 2014 Jan 16;15(1):1112-42. (PMID: 24441568)
Sci Rep. 2018 Jul 5;8(1):10207. (PMID: 29976989)
J Biol Chem. 2000 Oct 27;275(43):33193-6. (PMID: 10969064)
Methods Mol Biol. 2014;1174:247-62. (PMID: 24947387)
J Neurosci. 2001 May 1;21(9):2949-57. (PMID: 11312278)
J Biol Chem. 2001 Apr 6;276(14):11409-13. (PMID: 11148218)
Mol Pharmacol. 2014 Mar;85(3):388-96. (PMID: 24302560)
J Mol Signal. 2007 Mar 30;2:3. (PMID: 17394670)
Acta Pharmacol Sin. 2012 Mar;33(3):351-62. (PMID: 22266725)
Cell Mol Life Sci. 2019 Nov;76(22):4447-4459. (PMID: 31435698)
J Mol Biol. 2016 Sep 25;428(19):3850-68. (PMID: 27515397)
Neuron. 2014 Nov 19;84(4):821-34. (PMID: 25453842)
J Mol Biol. 2015 Jun 5;427(11):2039-2055. (PMID: 25772494)
Cell Signal. 2020 May;69:109547. (PMID: 31982549)
Nat Methods. 2010 Dec;7(12):973-5. (PMID: 21037589)
J Biol Chem. 2023 Nov;299(11):105269. (PMID: 37739036)
J Biol Chem. 2021 Jan-Jun;296:100325. (PMID: 33493514)
Mol Interv. 2002 Jun;2(3):168-84. (PMID: 14993377)
Semin Cell Dev Biol. 2011 Oct;22(8):834-41. (PMID: 21821139)
Annu Rev Biochem. 2018 Jun 20;87:897-919. (PMID: 29925258)
J Biol Chem. 2021 Jan-Jun;296:100702. (PMID: 33901492)
Int J Hematol. 2014 Jan;99(1):57-68. (PMID: 24307516)
Int Rev Cell Mol Biol. 2018;339:133-191. (PMID: 29776603)
Biomolecules. 2022 Aug 20;12(8):. (PMID: 36009047)
معلومات مُعتمدة: R01 GM140191 United States GM NIGMS NIH HHS; R01 MH111520 United States MH NIMH NIH HHS; U01 NS128537 United States NS NINDS NIH HHS; UF1 NS133763 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Activators of G protein Signaling 3; G proteins; GDI; GPCR; Macrophage migration; Optogenetics
تواريخ الأحداث: Date Created: 20240619 Latest Revision: 20240831
رمز التحديث: 20240831
مُعرف محوري في PubMed: PMC11185739
DOI: 10.1101/2024.06.04.597473
PMID: 38895415
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2024.06.04.597473