GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure
Abstract
:1. Introduction
2. β-Adrenergic Regulation of Cardiac Function
2.1. G Protein-Coupled Receptors
2.2. Cardiac β-Adrenergic Receptors
2.3. β-Adrenergic Receptor in HF
3. Pathophysiological Roles of GRK2 and GRK5 in the Heart
3.1. GRK Isoforms
3.2. Role of GRK2 and GRK5 in Cardiac Remodeling and Heart Failure
3.2.1. GRK2
3.2.2. GRK5
4. Role of Epac1 in Cardiac Pathophysiology
4.1. Epac Structure and Activation
4.2. Epac Pharmacological Tools
4.3. Role of Epac in Cardiac Disease
5. Epac1 and GRK Molecular Complex Formation in Cardiac Remodeling
5.1. Epac1, CaMKII and β-Arrestin Complex
5.2. Epac1 and GRK5
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Rockman, H.A.; Koch, W.J.; Lefkowitz, R.J. Seven-transmembrane-spanning receptors and heart function. Nature 2002, 415, 206–212. [Google Scholar] [CrossRef]
- Bers, D.M. Cardiac excitation-contraction coupling. Nature 2002, 415, 198–205. [Google Scholar] [CrossRef]
- Murga, C.; Arcones, A.C.; Cruces-Sande, M.; Briones, A.M.; Salaices, M.; Mayor, F. G Protein-Coupled Receptor Kinase 2 (GRK2) as a Potential Therapeutic Target in Cardiovascular and Metabolic Diseases. Front. Pharmacol. 2019, 10, 112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pfleger, J.; Gresham, K.; Koch, W.J. G protein-coupled receptor kinases as therapeutic targets in the heart. Nat. Rev. Cardiol. 2019, 16, 612–622. [Google Scholar] [CrossRef] [PubMed]
- El-Armouche, A.; Eschenhagen, T. Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail. Rev. 2009, 14, 225–241. [Google Scholar] [CrossRef] [PubMed]
- Laudette, M.; Coluccia, A.; Sainte-Marie, Y.; Solari, A.; Fazal, L.; Sicard, P.; Silvestri, R.; Mialet-Perez, J.; Pons, S.; Ghaleh, B.; et al. Identification of a pharmacological inhibitor of Epac1 that protects the heart against acute and chronic models of cardiac stress. Cardiovasc. Res. 2019, 115, 1766–1777. [Google Scholar] [CrossRef] [PubMed]
- Lezoualc’h, F.; Fazal, L.; Laudette, M.; Conte, C. Cyclic AMP Sensor EPAC Proteins and Their Role in Cardiovascular Function and Disease. Circ. Res. 2016, 118, 881–897. [Google Scholar] [CrossRef]
- Laurent, A.-C.; Bisserier, M.; Lucas, A.; Tortosa, F.; Roumieux, M.; de Régibus, A.; Swiader, A.; Sainte-Marie, Y.; Heymes, C.; Vindis, C.; et al. Exchange protein directly activated by cAMP 1 promotes autophagy during cardiomyocyte hypertrophy. Cardiovasc. Res. 2015, 105, 55–64. [Google Scholar] [CrossRef]
- Okumura, S.; Fujita, T.; Cai, W.; Jin, M.; Namekata, I.; Mototani, Y.; Jin, H.; Ohnuki, Y.; Tsuneoka, Y.; Kurotani, R.; et al. Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses. J. Clin. Investig 2014, 124, 2785–2801. [Google Scholar] [CrossRef] [Green Version]
- Métrich, M.; Lucas, A.; Gastineau, M.; Samuel, J.-L.; Heymes, C.; Morel, E.; Lezoualc’h, F. Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy. Circ. Res. 2008, 102, 959–965. [Google Scholar] [CrossRef] [Green Version]
- Rosenbaum, D.M.; Rasmussen, S.G.F.; Kobilka, B.K. The structure and function of G-protein-coupled receptors. Nature 2009, 459, 356–363. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pierce, K.L.; Premont, R.T.; Lefkowitz, R.J. Seven-transmembrane receptors. Nat. Rev. Mol. Cell Biol. 2002, 3, 639–650. [Google Scholar] [CrossRef] [PubMed]
- Clapham, D.E.; Neer, E.J. G protein beta gamma subunits. Annu. Rev. Pharmacol. Toxicol. 1997, 37, 167–203. [Google Scholar] [CrossRef]
- Wang, J.; Gareri, C.; Rockman, H.A. G-Protein-Coupled Receptors in Heart Disease. Circ. Res. 2018, 123, 716–735. [Google Scholar] [CrossRef] [PubMed]
- Syrovatkina, V.; Alegre, K.O.; Dey, R.; Huang, X.-Y. Regulation, Signaling, and Physiological Functions of G-Proteins. J. Mol. Biol. 2016, 428, 3850–3868. [Google Scholar] [CrossRef] [Green Version]
- Bobin, P.; Belacel-Ouari, M.; Bedioune, I.; Zhang, L.; Leroy, J.; Leblais, V.; Fischmeister, R.; Vandecasteele, G. Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective. Arch. Cardiovasc. Dis. 2016, 109, 431–443. [Google Scholar] [CrossRef]
- Formoso, K.; Lezoualc’h, F.; Mialet-Perez, J. Role of EPAC1 Signalosomes in Cell Fate: Friends or Foes? Cells 2020, 9, 1954. [Google Scholar] [CrossRef]
- Wettschureck, N.; Offermanns, S. Mammalian G proteins and their cell type specific functions. Physiol. Rev. 2005, 85, 1159–1204. [Google Scholar] [CrossRef] [Green Version]
- Myagmar, B.-E.; Flynn, J.M.; Cowley, P.M.; Swigart, P.M.; Montgomery, M.D.; Thai, K.; Nair, D.; Gupta, R.; Deng, D.X.; Hosoda, C.; et al. Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent. Circ. Res. 2017, 120, 1103–1115. [Google Scholar] [CrossRef] [Green Version]
- Lymperopoulos, A.; Rengo, G.; Koch, W.J. Adrenergic nervous system in heart failure: Pathophysiology and therapy. Circ. Res. 2013, 113, 739–753. [Google Scholar] [CrossRef]
- Balligand, J.-L. Cardiac salvage by tweaking with beta-3-adrenergic receptors. Cardiovasc. Res. 2016, 111, 128–133. [Google Scholar] [CrossRef]
- Liu, G.; Papa, A.; Katchman, A.N.; Zakharov, S.I.; Roybal, D.; Hennessey, J.A.; Kushner, J.; Yang, L.; Chen, B.-X.; Kushnir, A.; et al. Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics. Nature 2020, 577, 695–700. [Google Scholar] [CrossRef]
- Papa, A.; Kushner, J.S.; Hennessey, J.A.; Katchman, A.N.; Zakharov, S.I.; Chen, B.-X.; Yang, L.; Lu, R.; Leong, S.; Diaz, J.; et al. Adrenergic CaV1.2 Activation via Rad Phosphorylation Converges at α1C I-II Loop. Circ. Res. 2020. [Google Scholar] [CrossRef]
- De Lucia, C.; Eguchi, A.; Koch, W.J. New Insights in Cardiac β-Adrenergic Signaling During Heart Failure and Aging. Front. Pharmacol. 2018, 9, 904. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Woo, A.Y.-H.; Song, Y.; Xiao, R.-P.; Zhu, W. Biased β2-adrenoceptor signalling in heart failure: Pathophysiology and drug discovery. Br. J. Pharmacol. 2015, 172, 5444–5456. [Google Scholar] [CrossRef] [Green Version]
- Kuschel, M.; Zhou, Y.Y.; Cheng, H.; Zhang, S.J.; Chen, Y.; Lakatta, E.G.; Xiao, R.P. G(i) protein-mediated functional compartmentalization of cardiac beta(2)-adrenergic signaling. J. Biol. Chem. 1999, 274, 22048–22052. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rohrer, D.K.; Chruscinski, A.; Schauble, E.H.; Bernstein, D.; Kobilka, B.K. Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. J. Biol. Chem. 1999, 274, 16701–16708. [Google Scholar] [CrossRef] [Green Version]
- Baker, A.J. Adrenergic signaling in heart failure: A balance of toxic and protective effects. Pflugers Arch. 2014, 466, 1139–1150. [Google Scholar] [CrossRef]
- Berisha, F.; Nikolaev, V.O. Cyclic nucleotide imaging and cardiovascular disease. Pharmacol. Ther. 2017, 175, 107–115. [Google Scholar] [CrossRef]
- Nikolaev, V.O.; Moshkov, A.; Lyon, A.R.; Miragoli, M.; Novak, P.; Paur, H.; Lohse, M.J.; Korchev, Y.E.; Harding, S.E.; Gorelik, J. Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science 2010, 327, 1653–1657. [Google Scholar] [CrossRef]
- Yang, H.-Q.; Wang, L.-P.; Gong, Y.-Y.; Fan, X.-X.; Zhu, S.-Y.; Wang, X.-T.; Wang, Y.-P.; Li, L.-L.; Xing, X.; Liu, X.-X.; et al. β2-Adrenergic Stimulation Compartmentalizes β1 Signaling Into Nanoscale Local Domains by Targeting the C-Terminus of β1-Adrenoceptors. Circ. Res. 2019, 124, 1350–1359. [Google Scholar] [CrossRef] [PubMed]
- Shenoy, S.K.; Lefkowitz, R.J. β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol. Sci. 2011, 32, 521–533. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ahn, S.; Shenoy, S.K.; Luttrell, L.M.; Lefkowitz, R.J. SnapShot: β-Arrestin Functions. Cell 2020, 182, 1362-1352.e1. [Google Scholar] [CrossRef]
- Hill, J.A.; Olson, E.N. Cardiac plasticity. N. Engl. J. Med. 2008, 358, 1370–1380. [Google Scholar] [CrossRef] [PubMed]
- Bristow, M.R. Treatment of chronic heart failure with β-adrenergic receptor antagonists: A convergence of receptor pharmacology and clinical cardiology. Circ. Res. 2011, 109, 1176–1194. [Google Scholar] [CrossRef] [Green Version]
- De Lucia, C.; Femminella, G.D.; Gambino, G.; Pagano, G.; Allocca, E.; Rengo, C.; Silvestri, C.; Leosco, D.; Ferrara, N.; Rengo, G. Adrenal adrenoceptors in heart failure. Front. Physiol. 2014, 5, 246. [Google Scholar] [CrossRef] [Green Version]
- Von Lueder, T.G.; Krum, H. New medical therapies for heart failure. Nat. Rev. Cardiol. 2015, 12, 730–740. [Google Scholar] [CrossRef]
- Bristow, M.R.; Ginsburg, R.; Minobe, W.; Cubicciotti, R.S.; Sageman, W.S.; Lurie, K.; Billingham, M.E.; Harrison, D.C.; Stinson, E.B. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N. Engl. J. Med. 1982, 307, 205–211. [Google Scholar] [CrossRef]
- Engelhardt, S.; Böhm, M.; Erdmann, E.; Lohse, M.J. Analysis of beta-adrenergic receptor mRNA levels in human ventricular biopsy specimens by quantitative polymerase chain reactions: Progressive reduction of beta 1-adrenergic receptor mRNA in heart failure. J. Am. Coll. Cardiol. 1996, 27, 146–154. [Google Scholar] [CrossRef]
- Bristow, M.R.; Ginsburg, R.; Umans, V.; Fowler, M.; Minobe, W.; Rasmussen, R.; Zera, P.; Menlove, R.; Shah, P.; Jamieson, S. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: Coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ. Res. 1986, 59, 297–309. [Google Scholar] [CrossRef] [Green Version]
- Neumann, J.; Schmitz, W.; Scholz, H.; von Meyerinck, L.; Döring, V.; Kalmar, P. Increase in myocardial Gi-proteins in heart failure. Lancet Lond. Engl. 1988, 2, 936–937. [Google Scholar] [CrossRef]
- Froese, A.; Nikolaev, V.O. Imaging alterations of cardiomyocyte cAMP microdomains in disease. Front. Pharmacol. 2015, 6, 172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharpe, N. Benefit of beta-blockers for heart failure: Proven in 1999. Lancet Lond. Engl. 1999, 353, 1988–1989. [Google Scholar] [CrossRef]
- Flesch, M.; Ettelbrück, S.; Rosenkranz, S.; Maack, C.; Cremers, B.; Schlüter, K.D.; Zolk, O.; Böhm, M. Differential effects of carvedilol and metoprolol on isoprenaline-induced changes in beta-adrenoceptor density and systolic function in rat cardiac myocytes. Cardiovasc. Res. 2001, 49, 371–380. [Google Scholar] [CrossRef] [Green Version]
- Reiken, S.; Wehrens, X.H.T.; Vest, J.A.; Barbone, A.; Klotz, S.; Mancini, D.; Burkhoff, D.; Marks, A.R. Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Circulation 2003, 107, 2459–2466. [Google Scholar] [CrossRef]
- Gurevich, E.V.; Tesmer, J.J.G.; Mushegian, A.; Gurevich, V.V. G protein-coupled receptor kinases: More than just kinases and not only for GPCRs. Pharmacol. Ther. 2012, 133, 40–69. [Google Scholar] [CrossRef] [Green Version]
- Dzimiri, N.; Muiya, P.; Andres, E.; Al-Halees, Z. Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases. Eur. J. Pharmacol. 2004, 489, 167–177. [Google Scholar] [CrossRef]
- Montó, F.; Oliver, E.; Vicente, D.; Rueda, J.; Agüero, J.; Almenar, L.; Ivorra, M.D.; Barettino, D.; D’Ocon, P. Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure etiology and correlates to clinical variables. Am. J. Physiol. Heart Circ. Physiol. 2012, 303, H368–H376. [Google Scholar] [CrossRef] [Green Version]
- Schumacher, S.M.; Koch, W.J. Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling. J. Cardiovasc. Pharmacol. 2017, 70, 129–141. [Google Scholar] [CrossRef]
- Homan, K.T.; Wu, E.; Cannavo, A.; Koch, W.J.; Tesmer, J.J.G. Identification and characterization of amlexanox as a G protein-coupled receptor kinase 5 inhibitor. Molecules 2014, 19, 16937–16949. [Google Scholar] [CrossRef] [Green Version]
- Sato, P.Y.; Chuprun, J.K.; Schwartz, M.; Koch, W.J. The evolving impact of g protein-coupled receptor kinases in cardiac health and disease. Physiol. Rev. 2015, 95, 377–404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peterson, Y.K.; Luttrell, L.M. The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling. Pharmacol. Rev. 2017, 69, 256–297. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Penela, P.; Murga, C.; Ribas, C.; Tutor, A.S.; Peregrín, S.; Mayor, F. Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease. Cardiovasc. Res. 2006, 69, 46–56. [Google Scholar] [CrossRef]
- Penela, P.; Ribas, C.; Sánchez-Madrid, F.; Mayor, F. G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub. Cell. Mol. Life Sci. CMLS 2019, 76, 4423–4446. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rengo, G.; Lymperopoulos, A.; Leosco, D.; Koch, W.J. GRK2 as a novel gene therapy target in heart failure. J. Mol. Cell. Cardiol. 2011, 50, 785–792. [Google Scholar] [CrossRef] [Green Version]
- Chen, M.; Sato, P.Y.; Chuprun, J.K.; Peroutka, R.J.; Otis, N.J.; Ibetti, J.; Pan, S.; Sheu, S.-S.; Gao, E.; Koch, W.J. Prodeath signaling of G protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinase-dependent heat shock protein 90-mediated mitochondrial targeting. Circ. Res. 2013, 112, 1121–1134. [Google Scholar] [CrossRef] [Green Version]
- Sato, P.Y.; Chuprun, J.K.; Grisanti, L.A.; Woodall, M.C.; Brown, B.R.; Roy, R.; Traynham, C.J.; Ibetti, J.; Lucchese, A.M.; Yuan, A.; et al. Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation. Sci. Signal. 2018, 11. [Google Scholar] [CrossRef] [Green Version]
- Vinge, L.E.; Raake, P.W.; Koch, W.J. Gene therapy in heart failure. Circ. Res. 2008, 102, 1458–1470. [Google Scholar] [CrossRef]
- Penela, P.; Inserte, J.; Ramos, P.; Rodriguez-Sinovas, A.; Garcia-Dorado, D.; Mayor, F. Degradation of GRK2 and AKT is an early and detrimental event in myocardial ischemia/reperfusion. EBioMedicine 2019, 48, 605–618. [Google Scholar] [CrossRef] [Green Version]
- Leineweber, K.; Rohe, P.; Beilfuss, A.; Wolf, C.; Sporkmann, H.; Bruck, H.; Jakob, H.-G.; Heusch, G.; Philipp, T.; Brodde, O.-E. G-protein-coupled receptor kinase activity in human heart failure: Effects of beta-adrenoceptor blockade. Cardiovasc. Res. 2005, 66, 512–519. [Google Scholar] [CrossRef] [Green Version]
- Rengo, G.; Pagano, G.; Filardi, P.P.; Femminella, G.D.; Parisi, V.; Cannavo, A.; Liccardo, D.; Komici, K.; Gambino, G.; D’Amico, M.L.; et al. Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure. Circ. Res. 2016, 118, 1116–1124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lieu, M.; Koch, W.J. GRK2 and GRK5 as therapeutic targets and their role in maladaptive and pathological cardiac hypertrophy. Expert Opin. Ther. Targets 2019, 23, 201–214. [Google Scholar] [CrossRef] [PubMed]
- Koch, W.J.; Rockman, H.A.; Samama, P.; Hamilton, R.A.; Bond, R.A.; Milano, C.A.; Lefkowitz, R.J. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science 1995, 268, 1350–1353. [Google Scholar] [CrossRef] [PubMed]
- Brinks, H.; Boucher, M.; Gao, E.; Chuprun, J.K.; Pesant, S.; Raake, P.W.; Huang, Z.M.; Wang, X.; Qiu, G.; Gumpert, A.; et al. Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms. Circ. Res. 2010, 107, 1140–1149. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harding, V.B.; Jones, L.R.; Lefkowitz, R.J.; Koch, W.J.; Rockman, H.A. Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. Proc. Natl. Acad. Sci. USA 2001, 98, 5809–5814. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Suzuki, Y.; Nakano, K.; Sugiyama, M.; Imagawa, J. betaARK1 inhibition improves survival in a mouse model of heart failure induced by myocardial infarction. J. Cardiovasc. Pharmacol. 2004, 44, 329–334. [Google Scholar] [CrossRef] [PubMed]
- Eckhart, A.D.; Koch, W.J. Expression of a beta-adrenergic receptor kinase inhibitor reverses dysfunction in failing cardiomyocytes. Mol. Ther. J. Am. Soc. Gene Ther. 2002, 5, 74–79. [Google Scholar] [CrossRef]
- Rockman, H.A.; Chien, K.R.; Choi, D.J.; Iaccarino, G.; Hunter, J.J.; Ross, J.; Lefkowitz, R.J.; Koch, W.J. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl. Acad. Sci. USA 1998, 95, 7000–7005. [Google Scholar] [CrossRef] [Green Version]
- Bonacci, T.M.; Mathews, J.L.; Yuan, C.; Lehmann, D.M.; Malik, S.; Wu, D.; Font, J.L.; Bidlack, J.M.; Smrcka, A.V. Differential targeting of Gbetagamma-subunit signaling with small molecules. Science 2006, 312, 443–446. [Google Scholar] [CrossRef] [Green Version]
- Bernardo, B.C.; Blaxall, B.C. From Bench to Bedside: New Approaches to Therapeutic Discovery for Heart Failure. Heart Lung Circ. 2016, 25, 425–434. [Google Scholar] [CrossRef] [Green Version]
- Casey, L.M.; Pistner, A.R.; Belmonte, S.L.; Migdalovich, D.; Stolpnik, O.; Nwakanma, F.E.; Vorobiof, G.; Dunaevsky, O.; Matavel, A.; Lopes, C.M.B.; et al. Small molecule disruption of G beta gamma signaling inhibits the progression of heart failure. Circ. Res. 2010, 107, 532–539. [Google Scholar] [CrossRef] [Green Version]
- Kamal, F.A.; Mickelsen, D.M.; Wegman, K.M.; Travers, J.G.; Moalem, J.; Hammes, S.R.; Smrcka, A.V.; Blaxall, B.C. Simultaneous adrenal and cardiac g-protein-coupled receptor-gβγ inhibition halts heart failure progression. J. Am. Coll. Cardiol. 2014, 63, 2549–2557. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Travers, J.G.; Kamal, F.A.; Valiente-Alandi, I.; Nieman, M.L.; Sargent, M.A.; Lorenz, J.N.; Molkentin, J.D.; Blaxall, B.C. Pharmacological and Activated Fibroblast Targeting of Gβγ-GRK2 After Myocardial Ischemia Attenuates Heart Failure Progression. J. Am. Coll. Cardiol. 2017, 70, 958–971. [Google Scholar] [CrossRef] [PubMed]
- Schumacher, S.M.; Gao, E.; Zhu, W.; Chen, X.; Chuprun, J.K.; Feldman, A.M.; Tesmer, J.J.G.; Koch, W.J. Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction. Sci. Transl. Med. 2015, 7, 277ra31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rockman, H.A.; Choi, D.J.; Rahman, N.U.; Akhter, S.A.; Lefkowitz, R.J.; Koch, W.J. Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice. Proc. Natl. Acad. Sci. USA 1996, 93, 9954–9959. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martini, J.S.; Raake, P.; Vinge, L.E.; DeGeorge, B.R.; DeGeorge, B.; Chuprun, J.K.; Harris, D.M.; Gao, E.; Eckhart, A.D.; Pitcher, J.A.; et al. Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc. Natl. Acad. Sci. USA 2008, 105, 12457–12462. [Google Scholar] [CrossRef] [Green Version]
- Gold, J.I.; Gao, E.; Shang, X.; Premont, R.T.; Koch, W.J. Determining the absolute requirement of G protein-coupled receptor kinase 5 for pathological cardiac hypertrophy: Short communication. Circ. Res. 2012, 111, 1048–1053. [Google Scholar] [CrossRef]
- Johnson, L.R.; Scott, M.G.H.; Pitcher, J.A. G protein-coupled receptor kinase 5 contains a DNA-binding nuclear localization sequence. Mol. Cell. Biol. 2004, 24, 10169–10179. [Google Scholar] [CrossRef] [Green Version]
- Hullmann, J.E.; Grisanti, L.A.; Makarewich, C.A.; Gao, E.; Gold, J.I.; Chuprun, J.K.; Tilley, D.G.; Houser, S.R.; Koch, W.J. GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity. Circ. Res. 2014, 115, 976–985. [Google Scholar] [CrossRef] [Green Version]
- Johnson, L.R.; Robinson, J.D.; Lester, K.N.; Pitcher, J.A. Distinct structural features of G protein-coupled receptor kinase 5 (GRK5) regulate its nuclear localization and DNA-binding ability. PLoS ONE 2013, 8, e62508. [Google Scholar] [CrossRef] [Green Version]
- Traynham, C.J.; Hullmann, J.; Koch, W.J. Canonical and non-canonical actions of GRK5 in the heart. J. Mol. Cell. Cardiol. 2016, 92, 196–202. [Google Scholar] [CrossRef] [Green Version]
- Traynham, C.J.; Cannavo, A.; Zhou, Y.; Vouga, A.G.; Woodall, B.P.; Hullmann, J.; Ibetti, J.; Gold, J.I.; Chuprun, J.K.; Gao, E.; et al. Differential Role of G Protein-Coupled Receptor Kinase 5 in Physiological Versus Pathological Cardiac Hypertrophy. Circ. Res. 2015, 117, 1001–1012. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, C.H.; Lee, J.H.; Lee, M.Y.; Lee, J.H.; Lee, B.H.; Oh, K.-S. A novel role of G protein-coupled receptor kinase 5 in urotensin II-stimulated cellular hypertrophy in H9c2UT cells. Mol. Cell. Biochem. 2016, 422, 151–160. [Google Scholar] [CrossRef] [PubMed]
- Gloerich, M.; Bos, J.L. Epac: Defining a new mechanism for cAMP action. Annu. Rev. Pharmacol. Toxicol. 2010, 50, 355–375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Robichaux, W.G.; Cheng, X. Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development. Physiol. Rev. 2018, 98, 919–1053. [Google Scholar] [CrossRef]
- Bouvet, M.; Blondeau, J.-P.; Lezoualc’h, F. The Epac1 Protein: Pharmacological Modulators, Cardiac Signalosome and Pathophysiology. Cells 2019, 8, 1543. [Google Scholar] [CrossRef] [Green Version]
- White, M.A.; Tsalkova, T.; Mei, F.C.; Cheng, X. Conformational States of Exchange Protein Directly Activated by cAMP (EPAC1) Revealed by Ensemble Modeling and Integrative Structural Biology. Cells 2019, 9, 35. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Laudette, M.; Zuo, H.; Lezoualc’h, F.; Schmidt, M. Epac Function and cAMP Scaffolds in the Heart and Lung. J. Cardiovasc. Dev. Dis. 2018, 5, 9. [Google Scholar] [CrossRef] [Green Version]
- Ponsioen, B.; Zhao, J.; Riedl, J.; Zwartkruis, F.; van der Krogt, G.; Zaccolo, M.; Moolenaar, W.H.; Bos, J.L.; Jalink, K. Detecting cAMP-induced Epac activation by fluorescence resonance energy transfer: Epac as a novel cAMP indicator. EMBO Rep. 2004, 5, 1176–1180. [Google Scholar] [CrossRef] [Green Version]
- DiPilato, L.M.; Cheng, X.; Zhang, J. Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc. Natl. Acad. Sci. USA 2004, 101, 16513–16518. [Google Scholar] [CrossRef] [Green Version]
- Enserink, J.M.; Christensen, A.E.; de Rooij, J.; van Triest, M.; Schwede, F.; Genieser, H.G.; Døskeland, S.O.; Blank, J.L.; Bos, J.L. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat. Cell Biol. 2002, 4, 901–906. [Google Scholar] [CrossRef]
- Courilleau, D.; Bouyssou, P.; Fischmeister, R.; Lezoualc’h, F.; Blondeau, J.-P. The (R)-enantiomer of CE3F4 is a preferential inhibitor of human exchange protein directly activated by cyclic AMP isoform 1 (Epac1). Biochem. Biophys. Res. Commun. 2013, 440, 443–448. [Google Scholar] [CrossRef]
- Beck, E.M.; Parnell, E.; Cowley, A.; Porter, A.; Gillespie, J.; Robinson, J.; Robinson, L.; Pannifer, A.D.; Hamon, V.; Jones, P.; et al. Identification of A Novel Class of Benzofuran Oxoacetic Acid-Derived Ligands that Selectively Activate Cellular EPAC1. Cells 2019, 8, 1425. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, P.; Luchowska-Stańska, U.; van Basten, B.; Chen, H.; Liu, Z.; Wiejak, J.; Whelan, P.; Morgan, D.; Lochhead, E.; Barker, G.; et al. Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators. J. Med. Chem. 2020, 63, 5159–5184. [Google Scholar] [CrossRef] [PubMed]
- Courilleau, D.; Bisserier, M.; Jullian, J.-C.; Lucas, A.; Bouyssou, P.; Fischmeister, R.; Blondeau, J.-P.; Lezoualc’h, F. Identification of a tetrahydroquinoline analog as a pharmacological inhibitor of the cAMP-binding protein Epac. J. Biol. Chem. 2012, 287, 44192–44202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boulton, S.; Selvaratnam, R.; Blondeau, J.-P.; Lezoualc’h, F.; Melacini, G. Mechanism of Selective Enzyme Inhibition through Uncompetitive Regulation of an Allosteric Agonist. J. Am. Chem. Soc. 2018, 140, 9624–9637. [Google Scholar] [CrossRef]
- Morel, E.; Marcantoni, A.; Gastineau, M.; Birkedal, R.; Rochais, F.; Garnier, A.; Lompré, A.-M.; Vandecasteele, G.; Lezoualc’h, F. cAMP-binding protein Epac induces cardiomyocyte hypertrophy. Circ. Res. 2005, 97, 1296–1304. [Google Scholar] [CrossRef]
- Monceau, V.; Llach, A.; Azria, D.; Bridier, A.; Petit, B.; Mazevet, M.; Strup-Perrot, C.; To, T.-H.-V.; Calmels, L.; Germaini, M.-M.; et al. Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis. Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol. 2014, 111, 63–71. [Google Scholar] [CrossRef]
- Fazal, L.; Laudette, M.; Paula-Gomes, S.; Pons, S.; Conte, C.; Tortosa, F.; Sicard, P.; Sainte-Marie, Y.; Bisserier, M.; Lairez, O.; et al. Multifunctional Mitochondrial Epac1 Controls Myocardial Cell Death. Circ. Res. 2017, 120, 645–657. [Google Scholar] [CrossRef]
- Métrich, M.; Laurent, A.-C.; Breckler, M.; Duquesnes, N.; Hmitou, I.; Courillau, D.; Blondeau, J.-P.; Crozatier, B.; Lezoualc’h, F.; Morel, E. Epac activation induces histone deacetylase nuclear export via a Ras-dependent signalling pathway. Cell. Signal. 2010, 22, 1459–1468. [Google Scholar] [CrossRef]
- Pereira, L.; Rehmann, H.; Lao, D.H.; Erickson, J.R.; Bossuyt, J.; Chen, J.; Bers, D.M. Novel Epac fluorescent ligand reveals distinct Epac1 vs. Epac2 distribution and function in cardiomyocytes. Proc. Natl. Acad. Sci. USA 2015, 112, 3991–3996. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, M.-X.; Zheng, J.-K.; Wang, W.-W.; Kong, F.-Q.; Wu, X.-X.; Jiang, J.-K.; Pan, J.-X. Exchange-protein activated by cAMP (EPAC) regulates L-type calcium channel in atrial fibrillation of heart failure model. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 2200–2207. [Google Scholar] [CrossRef] [PubMed]
- Prajapati, R.; Fujita, T.; Suita, K.; Nakamura, T.; Cai, W.; Hidaka, Y.; Umemura, M.; Yokoyama, U.; Knollmann, B.C.; Okumura, S.; et al. Usefulness of Exchanged Protein Directly Activated by cAMP (Epac)1-Inhibiting Therapy for Prevention of Atrial and Ventricular Arrhythmias in Mice. Circ. J. Off. J. Jpn. Circ. Soc. 2019, 83, 295–303. [Google Scholar] [CrossRef]
- Aflaki, M.; Qi, X.-Y.; Xiao, L.; Ordog, B.; Tadevosyan, A.; Luo, X.; Maguy, A.; Shi, Y.; Tardif, J.-C.; Nattel, S. Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained β-adrenergic activation in guinea pig hearts. Circ. Res. 2014, 114, 993–1003. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Domínguez-Rodríguez, A.; Ruiz-Hurtado, G.; Sabourin, J.; Gómez, A.M.; Alvarez, J.L.; Benitah, J.-P. Proarrhythmic effect of sustained EPAC activation on TRPC3/4 in rat ventricular cardiomyocytes. J. Mol. Cell. Cardiol. 2015, 87, 74–78. [Google Scholar] [CrossRef] [PubMed]
- Shukla, A.K.; Westfield, G.H.; Xiao, K.; Reis, R.I.; Huang, L.-Y.; Tripathi-Shukla, P.; Qian, J.; Li, S.; Blanc, A.; Oleskie, A.N.; et al. Visualization of arrestin recruitment by a G-protein-coupled receptor. Nature 2014, 512, 218–222. [Google Scholar] [CrossRef]
- Mangmool, S.; Shukla, A.K.; Rockman, H.A. beta-Arrestin-dependent activation of Ca(2+)/calmodulin kinase II after beta(1)-adrenergic receptor stimulation. J. Cell Biol. 2010, 189, 573–587. [Google Scholar] [CrossRef] [Green Version]
- Berthouze-Duquesnes, M.; Lucas, A.; Saulière, A.; Sin, Y.Y.; Laurent, A.-C.; Galés, C.; Baillie, G.; Lezoualc’h, F. Specific interactions between Epac1, β-arrestin2 and PDE4D5 regulate β-adrenergic receptor subtype differential effects on cardiac hypertrophic signaling. Cell. Signal. 2013, 25, 970–980. [Google Scholar] [CrossRef]
- Dybkova, N.; Wagner, S.; Backs, J.; Hund, T.J.; Mohler, P.J.; Sowa, T.; Nikolaev, V.O.; Maier, L.S. Tubulin polymerization disrupts cardiac β-adrenergic regulation of late INa. Cardiovasc. Res. 2014, 103, 168–177. [Google Scholar] [CrossRef] [Green Version]
- Boccella, N.; Paolillo, R.; Perrino, C. Epac1 inhibition as a novel cardioprotective strategy: Lights and shadows on GRK5 canonical and non-canonical functions. Cardiovasc. Res. 2019, 115, 1684–1686. [Google Scholar] [CrossRef]
- Nuber, S.; Zabel, U.; Lorenz, K.; Nuber, A.; Milligan, G.; Tobin, A.B.; Lohse, M.J.; Hoffmann, C. β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle. Nature 2016, 531, 661–664. [Google Scholar] [CrossRef] [Green Version]
- Xu, B.; Li, M.; Wang, Y.; Zhao, M.; Morotti, S.; Shi, Q.; Wang, Q.; Barbagallo, F.; Teoh, J.-P.; Reddy, G.R.; et al. GRK5 Controls SAP97-Dependent Cardiotoxic β1 Adrenergic Receptor-CaMKII Signaling in Heart Failure. Circ. Res. 2020, 127, 796–810. [Google Scholar] [CrossRef] [PubMed]
- Zhu, W.-Z.; Wang, S.-Q.; Chakir, K.; Yang, D.; Zhang, T.; Brown, J.H.; Devic, E.; Kobilka, B.K.; Cheng, H.; Xiao, R.-P. Linkage of beta1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. J. Clin. Investig. 2003, 111, 617–625. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dewenter, M.; Neef, S.; Vettel, C.; Lämmle, S.; Beushausen, C.; Zelarayan, L.C.; Katz, S.; von der Lieth, A.; Meyer-Roxlau, S.; Weber, S.; et al. Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure. Circ. Heart Fail. 2017, 10, e003840. [Google Scholar] [CrossRef] [Green Version]
- Rokita, A.G.; Anderson, M.E. New therapeutic targets in cardiology: Arrhythmias and Ca2+/calmodulin-dependent kinase II (CaMKII). Circulation 2012, 126, 2125–2139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anderson, M.E.; Brown, J.H.; Bers, D.M. CaMKII in myocardial hypertrophy and heart failure. J. Mol. Cell. Cardiol. 2011, 51, 468–473. [Google Scholar] [CrossRef] [Green Version]
- Barella, L.F.; Rossi, M.; Zhu, L.; Cui, Y.; Mei, F.C.; Cheng, X.; Chen, W.; Gurevich, V.V.; Wess, J. β-Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion. J. Clin. Investig. 2019, 129, 3732–3737. [Google Scholar] [CrossRef]
- Singhmar, P.; Huo, X.; Eijkelkamp, N.; Berciano, S.R.; Baameur, F.; Mei, F.C.; Zhu, Y.; Cheng, X.; Hawke, D.; Mayor, F.; et al. Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1. Proc. Natl. Acad. Sci. USA 2016, 113, 3036–3041. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Fu, W.; Gong, X.; Chen, Z.; Tang, L.; Yang, D.; Liao, Q.; Xia, X.; Wu, H.; Liu, C.; et al. The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction. Eur. Heart J. 2020. [Google Scholar] [CrossRef]
- Nooh, M.M.; Chumpia, M.M.; Hamilton, T.B.; Bahouth, S.W. Sorting of β1-adrenergic receptors is mediated by pathways that are either dependent on or independent of type I PDZ, protein kinase A (PKA), and SAP97. J. Biol. Chem. 2014, 289, 2277–2294. [Google Scholar] [CrossRef] [Green Version]
- Fu, Q.; Kim, S.; Soto, D.; de Arcangelis, V.; DiPilato, L.; Liu, S.; Xu, B.; Shi, Q.; Zhang, J.; Xiang, Y.K. A long lasting β1 adrenergic receptor stimulation of cAMP/protein kinase A (PKA) signal in cardiac myocytes. J. Biol. Chem. 2014, 289, 14771–14781. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schmidt, M.; Evellin, S.; Weernink, P.A.; von Dorp, F.; Rehmann, H.; Lomasney, J.W.; Jakobs, K.H. A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nat. Cell Biol. 2001, 3, 1020–1024. [Google Scholar] [CrossRef] [PubMed]
- Nash, C.A.; Brown, L.M.; Malik, S.; Cheng, X.; Smrcka, A.V. Compartmentalized cyclic nucleotides have opposing effects on regulation of hypertrophic phospholipase Cε signaling in cardiac myocytes. J. Mol. Cell. Cardiol. 2018, 121, 51–59. [Google Scholar] [CrossRef]
- Pereira, L.; Ruiz-Hurtado, G.; Morel, E.; Laurent, A.-C.; Métrich, M.; Domínguez-Rodríguez, A.; Lauton-Santos, S.; Lucas, A.; Benitah, J.-P.; Bers, D.M.; et al. Epac enhances excitation-transcription coupling in cardiac myocytes. J. Mol. Cell. Cardiol. 2012, 52, 283–291. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, L.; Malik, S.; Pang, J.; Wang, H.; Park, K.M.; Yule, D.I.; Blaxall, B.C.; Smrcka, A.V. Phospholipase Cε hydrolyzes perinuclear phosphatidylinositol 4-phosphate to regulate cardiac hypertrophy. Cell 2013, 153, 216–227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hochbaum, D.; Tanos, T.; Ribeiro-Neto, F.; Altschuler, D.; Coso, O.A. Activation of JNK by Epac is independent of its activity as a Rap guanine nucleotide exchanger. J. Biol. Chem. 2003, 278, 33738–33746. [Google Scholar] [CrossRef] [Green Version]
- Shi, G.-X.; Rehmann, H.; Andres, D.A. A novel cyclic AMP-dependent Epac-Rit signaling pathway contributes to PACAP38-mediated neuronal differentiation. Mol. Cell. Biol. 2006, 26, 9136–9147. [Google Scholar] [CrossRef] [Green Version]
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Laudette, M.; Formoso, K.; Lezoualc’h, F. GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure. Cells 2021, 10, 154. https://doi.org/10.3390/cells10010154
Laudette M, Formoso K, Lezoualc’h F. GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure. Cells. 2021; 10(1):154. https://doi.org/10.3390/cells10010154
Chicago/Turabian StyleLaudette, Marion, Karina Formoso, and Frank Lezoualc’h. 2021. "GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure" Cells 10, no. 1: 154. https://doi.org/10.3390/cells10010154
APA StyleLaudette, M., Formoso, K., & Lezoualc’h, F. (2021). GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure. Cells, 10(1), 154. https://doi.org/10.3390/cells10010154