دورية أكاديمية
Gi-coupled receptor activation potentiates Piezo2 currents via Gβγ.
العنوان: | Gi-coupled receptor activation potentiates Piezo2 currents via Gβγ. |
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المؤلفون: | Del Rosario JS; Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ, USA., Yudin Y; Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ, USA., Su S; Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ, USA., Hartle CM; Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, PA, USA., Mirshahi T; Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, PA, USA., Rohacs T; Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ, USA. |
المصدر: | EMBO reports [EMBO Rep] 2020 May 06; Vol. 21 (5), pp. e49124. Date of Electronic Publication: 2020 Mar 29. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2024- : [London] : Nature Publishing Group Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000- |
مواضيع طبية MeSH: | Ganglia, Spinal*/metabolism , Phosphatidylinositol 3-Kinases*, Animals ; Ion Channels/genetics ; Mice ; Neurons/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism |
مستخلص: | Mechanically activated Piezo2 channels are key players in somatosensory touch, but their regulation by cellular signaling pathways is poorly understood. Dorsal root ganglion (DRG) neurons express a variety of G-protein-coupled receptors that modulate the function of sensory ion channels. Gi-coupled receptors are generally considered inhibitory, as they usually decrease excitability. Paradoxically, activation of Gi-coupled receptors in DRG neurons sometimes induces mechanical hypersensitivity, the mechanism of which is not well understood. Here, we find that activation of Gi-coupled receptors potentiates mechanically activated currents in DRG neurons and heterologously expressed Piezo2 channels, but inhibits Piezo1 currents in heterologous systems in a Gβγ-dependent manner. Pharmacological inhibition of kinases downstream of Gβγ, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) also abolishes the potentiation of Piezo2 currents. Local injection of sumatriptan, an agonist of the Gi-coupled serotonin 1B/1D receptors, increases mechanical sensitivity in mice, and the effect is abolished by inhibiting PI3K and MAPK. Hence, our studies illustrate an indirect mechanism of action of Gβγ to sensitize Piezo2 currents and alter mechanosensitivity after activation of Gi-coupled receptors. (© 2020 The Authors.) |
References: | Front Mol Neurosci. 2014 Nov 11;7:87. (PMID: 25426020) Cell Rep. 2017 Nov 28;21(9):2357-2366. (PMID: 29186675) Nat Commun. 2019 Mar 13;10(1):1200. (PMID: 30867417) Nat Commun. 2013;4:1682. (PMID: 23575686) Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17547-17555. (PMID: 31413193) Nat Neurosci. 2017 Jan;20(1):24-33. (PMID: 27893727) Elife. 2018 Mar 09;7:. (PMID: 29521261) Can J Exp Psychol. 2003 Sep;57(3):167-75. (PMID: 14596475) J Physiol. 2011 Dec 15;589(Pt 24):6007-27. (PMID: 22005680) Neuroscience. 2018 Dec 1;394:60-71. (PMID: 30342200) Biophys Chem. 2016 Jan;208:26-33. (PMID: 26259784) Front Pharmacol. 2015 Jul 24;6:155. (PMID: 26257653) Cell Rep. 2018 Apr 17;23(3):701-708. (PMID: 29669276) Headache. 2012 May;52(5):773-84. (PMID: 22289052) Science. 2018 May 4;360(6388):530-533. (PMID: 29724954) Elife. 2017 Aug 15;6:. (PMID: 28826490) Pain. 2014 Jun;155(6):1150-60. (PMID: 24631588) Adv Pharmacol. 2010;58:123-47. (PMID: 20655481) Mol Brain. 2013 Dec 17;6:57. (PMID: 24344923) PLoS One. 2015 Oct 13;10(10):e0139957. (PMID: 26460749) Nature. 2014 Dec 4;516(7529):121-5. (PMID: 25471886) EMBO J. 2005 Dec 21;24(24):4211-23. (PMID: 16319926) Am J Med Genet A. 2017 Jan;173(1):254-259. (PMID: 27714920) Sci Signal. 2015 Feb 10;8(363):ra15. (PMID: 25670203) Clin Genet. 2017 Mar;91(3):470-475. (PMID: 27607563) Science. 1997 Jan 17;275(5298):394-7. (PMID: 8994038) Sci Transl Med. 2018 Oct 10;10(462):. (PMID: 30305456) Elife. 2015 May 22;4:. (PMID: 26001275) Life Sci. 2004 Apr 9;74(21):2643-53. (PMID: 15041446) Nature. 2017 Jan 12;541(7636):176-181. (PMID: 28002412) J Biol Chem. 2002 Mar 1;277(9):7348-55. (PMID: 11707461) EMBO Rep. 2020 May 6;21(5):e49124. (PMID: 32227462) Pharmacol Rev. 2013 Feb 13;65(2):545-77. (PMID: 23406670) Cell Rep. 2017 Dec 5;21(10):2760-2771. (PMID: 29212024) Nature. 1987 Jan 22-28;325(6102):321-6. (PMID: 2433589) Am J Physiol Cell Physiol. 2019 May 1;316(5):C741-C752. (PMID: 30811222) Annu Rev Pharmacol Toxicol. 1997;37:167-203. (PMID: 9131251) Science. 2010 Oct 1;330(6000):55-60. (PMID: 20813920) Nat Commun. 2015 May 26;6:7223. (PMID: 26008989) N Engl J Med. 2016 Oct 6;375(14):1355-1364. (PMID: 27653382) J Neurosci. 2019 Jul 31;39(31):6067-6080. (PMID: 31127000) Pain. 2016 Aug;157(8):1773-82. (PMID: 27075428) Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4667-72. (PMID: 23487782) Cell Rep. 2012 Sep 27;2(3):511-7. (PMID: 22921401) Mol Pain. 2018 Jan-Dec;14:1744806918763646. (PMID: 29580154) Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9284-7. (PMID: 7568118) Cell Rep. 2017 Dec 12;21(11):3102-3115. (PMID: 29241539) Br J Pharmacol. 1986 Dec;89(4):661-72. (PMID: 2434174) Nat Neurosci. 2015 Jan;18(1):145-53. (PMID: 25420068) Nature. 1994 Jul 14;370(6485):143-6. (PMID: 8022483) Neuropharmacology. 2012 Sep;63(3):362-7. (PMID: 22691374) Annu Rev Physiol. 1997;59:621-31. (PMID: 9074780) EMBO J. 2006 Jun 7;25(11):2368-76. (PMID: 16675954) Cell. 2015 Feb 12;160(4):759-770. (PMID: 25679765) Nat Neurosci. 2015 Dec;18(12):1756-62. (PMID: 26551544) Elife. 2017 Aug 15;6:. (PMID: 28826482) Sci Transl Med. 2018 Oct 10;10(462):. (PMID: 30305457) Science. 2018 Oct 26;362(6413):464-467. (PMID: 30361375) Physiol Rev. 2015 Apr;95(2):377-404. (PMID: 25834229) Elife. 2017 Aug 15;6:. (PMID: 28829742) |
معلومات مُعتمدة: | R01 NS055159 United States NS NINDS NIH HHS; F99 NS113422 United States NS NINDS NIH HHS; R01 GM111913 United States GM NIGMS NIH HHS; F31 NS100484 United States NS NINDS NIH HHS; R01 GM093290 United States GM NIGMS NIH HHS; R01 GM131048 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: MAPK; G-protein βγ; Gi-coupled receptors; PI3K; Piezo2 |
المشرفين على المادة: | 0 (Ion Channels) 0 (Piezo1 protein, mouse) 0 (Piezo2 protein, mouse) 0 (Receptors, G-Protein-Coupled) |
تواريخ الأحداث: | Date Created: 20200401 Date Completed: 20210427 Latest Revision: 20220531 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7202211 |
DOI: | 10.15252/embr.201949124 |
PMID: | 32227462 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1469-3178 |
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DOI: | 10.15252/embr.201949124 |