Cell swelling enhances ligand-driven β-adrenergic signaling.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 Sep 2024
07 Sep 2024
Historique:
received:
16
09
2023
accepted:
29
08
2024
medline:
7
9
2024
pubmed:
7
9
2024
entrez:
6
9
2024
Statut:
epublish
Résumé
G protein-coupled receptors' conformational landscape can be affected by their local, microscopic interactions within the cell plasma membrane. We employ here a pleiotropic stimulus, namely osmotic swelling, to alter the cortical environment within intact cells and monitor the response in terms of receptor function and downstream signaling. We observe that in osmotically swollen cells the β2-adrenergic receptor, a prototypical GPCR, favors an active conformation, resulting in cAMP transient responses to adrenergic stimulation that have increased amplitude. The results are validated in primary cell types such as adult cardiomyocytes, a model system where swelling occurs upon ischemia-reperfusion injury. Our results suggest that receptors' function is finely modulated by their biophysical context, and specifically that osmotic swelling acts as a potentiator of downstream signaling, not only for the β2-adrenergic receptor, but also for other receptors, hinting at a more general regulatory mechanism.
Identifiants
pubmed: 39242606
doi: 10.1038/s41467-024-52191-y
pii: 10.1038/s41467-024-52191-y
doi:
Substances chimiques
Receptors, Adrenergic, beta-2
0
Ligands
0
Cyclic AMP
E0399OZS9N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7822Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 421152132
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 421152132
Organisme : Leverhulme Trust
ID : RL-2022-015
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP24K21281
Organisme : MEXT | Japan Science and Technology Agency (JST)
ID : JPMJFR215T
Organisme : MEXT | Japan Science and Technology Agency (JST)
ID : JPMJMS2023
Organisme : University of St Andrews
ID : World Leading PhD fellowship
Informations de copyright
© 2024. The Author(s).
Références
De Lean, A., Stadel, J. M. & Lefkowitz, R. J. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J. Biol. Chem. 255, 7108–7117 (1980).
pubmed: 6248546
doi: 10.1016/S0021-9258(20)79672-9
Shukla, A. K., Singh, G. & Ghosh, E. Emerging structural insights into biased GPCR signaling. Trends Biochem. Sci. 39, 594–602 (2014).
pubmed: 25458114
doi: 10.1016/j.tibs.2014.10.001
Leach, K., Sexton, P. M. & Christopoulos, A. Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology. Trends Pharmacol. Sci. 28, 382–389 (2007).
pubmed: 17629965
doi: 10.1016/j.tips.2007.06.004
Hay, D. L., Poyner, D. R. & Sexton, P. M. GPCR modulation by RAMPs. Pharmacol. Ther. 109, 173–197 (2006).
pubmed: 16111761
doi: 10.1016/j.pharmthera.2005.06.015
Oates, J. & Watts, A. Uncovering the intimate relationship between lipids, cholesterol and GPCR activation. Curr. Opin. Struct. Biol. 21, 802–807 (2011).
pubmed: 22036833
doi: 10.1016/j.sbi.2011.09.007
Cao, T. T., Deacon, H. W., Reczek, D., Bretscher, A. & von Zastrow, M. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature 401, 286–290 (1999).
pubmed: 10499588
doi: 10.1038/45816
Soubias, O., Teague, W. E., Hines, K. G. & Gawrisch, K. The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors. Biochimie 107, 28–32 (2014).
pubmed: 25447139
pmcid: 4308488
doi: 10.1016/j.biochi.2014.10.011
Rosholm, K. R. et al. Membrane curvature regulates ligand-specific membrane sorting of GPCRs in living cells. Nat. Chem. Biol. 13, 724–729 (2017).
pubmed: 28481347
doi: 10.1038/nchembio.2372
Bathe-Peters, M. et al. Visualization of beta-adrenergic receptor dynamics and differential localization in cardiomyocytes. Proc Natl Acad Sci USA https://doi.org/10.1073/pnas.2101119118 (2021).
Calebiro, D. et al. Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol. 7, e1000172 (2009).
pubmed: 19688034
pmcid: 2718703
doi: 10.1371/journal.pbio.1000172
Kockelkoren, G. et al. Molecular mechanism of GPCR spatial organization at the plasma membrane. Nat. Chem. Biol. 20, 142–150 (2024).
pubmed: 37460675
doi: 10.1038/s41589-023-01385-4
Ostrom, R. S. & Insel, P. A. The evolving role of lipid rafts and caveolae in G protein-coupled receptor signaling: implications for molecular pharmacology. Br. J. Pharmacol. 143, 235–245 (2004).
pubmed: 15289291
pmcid: 1575337
doi: 10.1038/sj.bjp.0705930
Romero, G., von Zastrow, M. & Friedman, P. A. Role of PDZ proteins in regulating trafficking, signaling, and function of GPCRs: means, motif, and opportunity. Adv. Pharmacol. 62, 279–314 (2011).
pubmed: 21907913
pmcid: 4968410
doi: 10.1016/B978-0-12-385952-5.00003-8
Scarselli, M. et al. Revealing G-protein-coupled receptor oligomerization at the single-molecule level through a nanoscopic lens: methods, dynamics and biological function. FEBS J. 283, 1197–1217 (2016).
pubmed: 26509747
doi: 10.1111/febs.13577
Hardman, K., Goldman, A. & Pliotas, C. Membrane force reception: mechanosensation in G protein-coupled receptors and tools to address it. Curr. Opin. Physiol. https://doi.org/10.1016/j.cophys.2023.100689 (2023).
Chachisvilis, M., Zhang, Y. L. & Frangos, J. A. G protein-coupled receptors sense fluid shear stress in endothelial cells. Proc. Natl Acad. Sci. USA 103, 15463–15468 (2006).
pubmed: 17030791
pmcid: 1622845
doi: 10.1073/pnas.0607224103
Zou, Y. et al. Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat. Cell Biol. 6, 499–506 (2004).
pubmed: 15146194
doi: 10.1038/ncb1137
Erdogmus, S. et al. Helix 8 is the essential structural motif of mechanosensitive GPCRs. Nat. Commun. 10, 5784 (2019).
pubmed: 31857598
pmcid: 6923424
doi: 10.1038/s41467-019-13722-0
Hoffmann, E. K., Lambert, I. H. & Pedersen, S. F. Physiology of cell volume regulation in vertebrates. Physiol. Rev. 89, 193–277 (2009).
pubmed: 19126758
doi: 10.1152/physrev.00037.2007
Roffay, C. et al. Passive coupling of membrane tension and cell volume during active response of cells to osmosis. Proc Natl Acad Sci USA https://doi.org/10.1073/pnas.2103228118 (2021).
Liu, X. et al. Structural insights into the process of GPCR-G protein complex formation. Cell 177, 1243–1251.e1212 (2019).
pubmed: 31080070
pmcid: 6991123
doi: 10.1016/j.cell.2019.04.021
Scarselli, M., Annibale, P. & Radenovic, A. Cell type-specific beta2-adrenergic receptor clusters identified using photoactivated localization microscopy are not lipid raft related, but depend on actin cytoskeleton integrity. J. Biol. Chem. 287, 16768–16780 (2012).
pubmed: 22442147
pmcid: 3351334
doi: 10.1074/jbc.M111.329912
Klarenbeek, J., Goedhart, J., van Batenburg, A., Groenewald, D. & Jalink, K. Fourth-generation epac-based FRET sensors for cAMP feature exceptional brightness, photostability and dynamic range: characterization of dedicated sensors for FLIM, for ratiometry and with high affinity. PLoS ONE 10, e0122513 (2015).
pubmed: 25875503
pmcid: 4397040
doi: 10.1371/journal.pone.0122513
van Unen, J. et al. A new generation of FRET sensors for robust measurement of Galphai1, Galphai2 and Galphai3 activation kinetics in single cells. PLoS ONE 11, e0146789 (2016).
pubmed: 26799488
pmcid: 4723041
doi: 10.1371/journal.pone.0146789
Vandenberg, J. I., Rees, S. A., Wright, A. R. & Powell, T. Cell swelling and ion transport pathways in cardiac myocytes. Cardiovasc. Res. 32, 85–97 (1996).
pubmed: 8776406
doi: 10.1016/S0008-6363(96)00048-X
Drake, M. T., Shenoy, S. K. & Lefkowitz, R. J. Trafficking of G protein-coupled receptors. Circ. Res. 99, 570–582 (2006).
pubmed: 16973913
doi: 10.1161/01.RES.0000242563.47507.ce
Beavo, J. A. et al. Effects of xanthine derivatives on lipolysis and on adenosine 3’,5’-monophosphate phosphodiesterase activity. Mol. Pharmacol. 6, 597–603 (1970).
pubmed: 4322367
Tesmer, J. J., Sunahara, R. K., Gilman, A. G. & Sprang, S. R. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science 278, 1907–1916 (1997).
pubmed: 9417641
doi: 10.1126/science.278.5345.1907
Sunahara, R. K., Dessauer, C. W., Whisnant, R. E., Kleuss, C. & Gilman, A. G. Interaction of Gsalpha with the cytosolic domains of mammalian adenylyl cyclase. J. Biol. Chem. 272, 22265–22271 (1997).
pubmed: 9268375
doi: 10.1074/jbc.272.35.22265
Vortherms, T. A., Nguyen, C. H., Bastepe, M., Juppner, H. & Watts, V. J. D2 dopamine receptor-induced sensitization of adenylyl cyclase type 1 is G alpha(s) independent. Neuropharmacology 50, 576–584 (2006).
pubmed: 16376953
doi: 10.1016/j.neuropharm.2005.11.004
Stallaert, W. et al. Purinergic receptor transactivation by the beta(2)-adrenergic receptor increases intracellular Ca(2+) in nonexcitable cells. Mol. Pharmacol. 91, 533–544 (2017).
pubmed: 28280061
doi: 10.1124/mol.116.106419
Westfield, G. H. et al. Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex. Proc. Natl Acad. Sci. USA 108, 16086–16091 (2011).
pubmed: 21914848
pmcid: 3179071
doi: 10.1073/pnas.1113645108
Axelrod, D. Total internal reflection fluorescence microscopy. Methods Cell Biol. 30, 245–270 (1989).
pubmed: 2648112
doi: 10.1016/S0091-679X(08)60982-6
Nygaard, R. et al. The dynamic process of beta(2)-adrenergic receptor activation. Cell 152, 532–542 (2013).
pubmed: 23374348
pmcid: 3586676
doi: 10.1016/j.cell.2013.01.008
Lakowicz, J. R. Principles of Fluorescence Spectroscopy. 2nd edn (Kluwer Academic/Plenum, 1999).
Rasmussen, S. G. et al. Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor. Nature 469, 175–180 (2011).
pubmed: 21228869
pmcid: 3058308
doi: 10.1038/nature09648
Koster, D. V. & Mayor, S. Cortical actin and the plasma membrane: inextricably intertwined. Curr. Opin. Cell Biol. 38, 81–89 (2016).
pubmed: 26986983
doi: 10.1016/j.ceb.2016.02.021
Haussinger, D. The role of cellular hydration in the regulation of cell function. Biochem. J. 313, 697–710 (1996).
pubmed: 8611144
pmcid: 1216967
doi: 10.1042/bj3130697
Tang, W., Strachan, R. T., Lefkowitz, R. J. & Rockman, H. A. Allosteric modulation of beta-arrestin-biased angiotensin II type 1 receptor signaling by membrane stretch. J. Biol. Chem. 289, 28271–28283 (2014).
pubmed: 25170081
pmcid: 4192482
doi: 10.1074/jbc.M114.585067
Groulx, N., Boudreault, F., Orlov, S. N. & Grygorczyk, R. Membrane reserves and hypotonic cell swelling. J. Membr. Biol. 214, 43–56 (2006).
pubmed: 17598067
doi: 10.1007/s00232-006-0080-8
Lang, F. et al. Functional significance of cell volume regulatory mechanisms. Physiol. Rev. 78, 247–306 (1998).
pubmed: 9457175
doi: 10.1152/physrev.1998.78.1.247
Sinha, B. et al. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144, 402–413 (2011).
pubmed: 21295700
pmcid: 3042189
doi: 10.1016/j.cell.2010.12.031
Steinberg, S. F. beta(2)-Adrenergic receptor signaling complexes in cardiomyocyte caveolae/lipid rafts. J. Mol. Cell. Cardiol. 37, 407–415 (2004).
pubmed: 15276011
doi: 10.1016/j.yjmcc.2004.04.018
Allen, J. A. et al. Caveolin-1 and lipid microdomains regulate Gs trafficking and attenuate Gs/adenylyl cyclase signaling. Mol. Pharmacol. 76, 1082–1093 (2009).
pubmed: 19696145
pmcid: 2774991
doi: 10.1124/mol.109.060160
Guo, Y., Yang, L., Haught, K. & Scarlata, S. Osmotic stress reduces Ca2+ signals through deformation of caveolae. J. Biol. Chem. 290, 16698–16707 (2015).
pubmed: 25957403
pmcid: 4505420
doi: 10.1074/jbc.M115.655126
DiPilato, L. M. & Zhang, J. The role of membrane microdomains in shaping beta2-adrenergic receptor-mediated cAMP dynamics. Mol. Biosyst. 5, 832–837 (2009).
pubmed: 19603118
doi: 10.1039/b823243a
Irannejad, R. et al. Conformational biosensors reveal GPCR signalling from endosomes. Nature 495, 534–538 (2013).
pubmed: 23515162
doi: 10.1038/nature12000
Fried, S. D. E. et al. Hydration-mediated G-protein-coupled receptor activation. Proc. Natl Acad. Sci. USA 119, e2117349119 (2022).
pubmed: 35584119
pmcid: 9173805
doi: 10.1073/pnas.2117349119
Tolkovsky, A. M. & Levitzki, A. Mode of coupling between the beta-adrenergic receptor and adenylate cyclase in turkey erythrocytes. Biochemistry 17, 3795 (1978).
pubmed: 212105
doi: 10.1021/bi00611a020
Pena-Rasgado, C., Kimler, V. A., McGruder, K. D., Tie, J. & Rasgado-Flores, H. Opposite roles of cAMP and cGMP on volume loss in muscle cells. Am. J. Physiol. 267, C1319–C1328 (1994).
pubmed: 7977695
doi: 10.1152/ajpcell.1994.267.5.C1319
Meng, X. J. & Weinman, S. A. cAMP- and swelling-activated chloride conductance in rat hepatocytes. Am. J. Physiol. 271, C112–C120 (1996).
pubmed: 8760036
doi: 10.1152/ajpcell.1996.271.1.C112
Carpenter, E. & Peers, C. Swelling- and cAMP-activated Cl- currents in isolated rat carotid body type I cells. J. Physiol. 503, 497–511 (1997).
pubmed: 9379407
pmcid: 1159837
doi: 10.1111/j.1469-7793.1997.497bg.x
Golstein, P. E. et al. Hypotonic cell swelling stimulates permeability to cAMP in a rat colonic cell line. Pflug. Arch. 447, 845–854 (2004).
doi: 10.1007/s00424-003-1216-7
Hynes, T. R., Mervine, S. M., Yost, E. A., Sabo, J. L. & Berlot, C. H. Live cell imaging of Gs and the beta2-adrenergic receptor demonstrates that both alphas and beta1gamma7 internalize upon stimulation and exhibit similar trafficking patterns that differ from that of the beta2-adrenergic receptor. J. Biol. Chem. 279, 44101–44112 (2004).
pubmed: 15297467
doi: 10.1074/jbc.M405151200
Gmach, P., Bathe-Peters, M., Telugu, N., Miller, D. C. & Annibale, P. Fluorescence spectroscopy of low-level endogenous beta-adrenergic receptor expression at the plasma membrane of differentiating human iPSC-derived cardiomyocytes. Int. J. Mol. Sci. https://doi.org/10.3390/ijms231810405 (2022).
Bathe-Peters, M., Gmach, P., Annibale, P. & Lohse, M. J. Linescan microscopy data to extract diffusion coefficient of a fluorescent species using a commercial confocal microscope. Data Brief. 29, 105063 (2020).
pubmed: 32055652
pmcid: 7005367
doi: 10.1016/j.dib.2019.105063
Jaqaman, K. et al. Robust single-particle tracking in live-cell time-lapse sequences. Nat. Methods 5, 695–702 (2008).
pubmed: 18641657
pmcid: 2747604
doi: 10.1038/nmeth.1237