Encyclopedia of Computational Neuroscience

Living Edition
| Editors: Dieter Jaeger, Ranu Jung

Metabotropic Receptors (G Protein-Coupled Receptors)

Living reference work entry

Latest version View entry history

DOI: https://doi.org/10.1007/978-1-4614-7320-6_190-2

Synonyms

Definition

G protein-coupled receptors (GPCRs) are a large and important class of eukaryotic membrane receptors that bind extracellular ligands (molecules as diverse as odorants, hormones, pheromones, photons, neurotransmitters, and small molecule drugs) and transmit those cues to networks of intracellular signaling molecules ultimately driving and modulating cellular response. Mathematical modeling of GPCR signaling provides a platform to elucidate the mechanisms by which GPCR signaling carries out normal cellular function and, in disease states, what aspects of the system are perturbed.

Detailed Description

The wide variety of GPCR receptor species (>800 genes (Venter et al. 2001; Howard et al. 2001)), their diverse cellular...

Keywords

Adenosine Oligomerization NMDA Monophosphate Serpentine 
This is a preview of subscription content, log in to check access

References

  1. Andrews SS (2012) Spatial and stochastic cellular modeling with the Smoldyn simulator. In: van Helden J, Toussaint A, Thieffry D (eds) Bacterial molecular networks: methods and protocols, vol 804, Methods in molecular biology. Springer, New York, pp 519–542CrossRefGoogle Scholar
  2. Andrews SS, Addy NJ, Brent R, Arkin AP (2010) Detailed simulations of cell biology with Smoldyn 2.1. PLoS Comput Biol 6(3):e1000705PubMedCentralPubMedCrossRefGoogle Scholar
  3. Benedict KF, Lauffenburger DA (2013) Insights into proteomic immune cell signaling and communication via data-driven modeling. Curr Top Microbiol Immunol 363:201–233. doi:10.1007/82_2012_249PubMedGoogle Scholar
  4. Bhalla US (2004a) Signaling in small subcellular volumes. I. Stochastic and diffusion effects on individual pathways. Biophys J 87(2):733–744. doi:10.1529/biophysj.104.040469PubMedCentralPubMedCrossRefGoogle Scholar
  5. Bhalla US (2004b) Signaling in small subcellular volumes. II. Stochastic and diffusion effects on synaptic network properties. Biophys J 87(2):745–753. doi:10.1529/biophysj.104.040501PubMedCentralPubMedCrossRefGoogle Scholar
  6. Blackwell KT (2013) Approaches and tools for modeling signaling pathways and calcium dynamics in neurons. J Neurosci Method 220(2):131–140. doi:10.1016/j.jneumeth.2013.05.008Google Scholar
  7. Blackwell KT, Wallace LJ, Kim B, Oliveira RF, Koh W (2013) Modeling spatial aspects of intracellular dopamine signaling. Method Mol Biol (Clifton, NJ) 964:61–75. doi:10.1007/978-1-62703-251-3_5CrossRefGoogle Scholar
  8. Brinkerhoff CJ, Woolf PJ, Linderman JJ (2004) Monte Carlo simulations of receptor dynamics: insights into cell signaling. J Mol Histol 35(7):667–677PubMedGoogle Scholar
  9. Chakrabarty A, Buzzard GT, Rundell AE (2013) Model-based design of experiments for cellular processes. Wiley Interdiscip Rev Syst Biol Med 5(2):181–203. doi:10.1002/wsbm.1204PubMedCrossRefGoogle Scholar
  10. Cowan AE, Moraru II, Schaff JC, Slepchenko BM, Loew LM (2012) Spatial modeling of cell signaling networks. Method Cell Biol 110:195–221. doi:10.1016/b978-0-12-388403-9.00008-4CrossRefGoogle Scholar
  11. Fallahi-Sichani M, Linderman JJ (2009) Lipid raft-mediated regulation of G-protein coupled receptor signaling by ligands which influence receptor dimerization: a computational study. PLoS One 4(8)Google Scholar
  12. Fernandez É, Schiappa R, Girault J-A, Novère NL (2006) DARPP-32 is a robust integrator of dopamine and glutamate signals. PLoS Comput Biol 2(12):e176. doi:10.1371/journal.pcbi.0020176PubMedCentralPubMedCrossRefGoogle Scholar
  13. Filizola M, Weinstein H (2005) The study of G-protein coupled receptor oligomerization with computational modeling and bioinformatics. FEBS J 272(12):2926–2938. doi:10.1111/j.1742-4658.2005.04730.xPubMedCrossRefGoogle Scholar
  14. Grossfield A (2011) Recent progress in the study of G protein-coupled receptors with molecular dynamics computer simulations. Biochim Biophys Acta 1808(7):1868–1878. doi:10.1016/j.bbamem.2011.03.010PubMedCrossRefGoogle Scholar
  15. Howard AD, McAllister G, Feighner SD, Liu Q, Nargund RP, Van der Ploeg LHT, Patchett AA (2001) Orphan G-protein-coupled receptors and natural ligand discovery. Trends Pharmacol Sci 22(3):132–140. doi:10.1016/S0165-6147(00)01636-9PubMedCrossRefGoogle Scholar
  16. Janes KA, Yaffe MB (2006) Data-driven modelling of signal-transduction networks. Nat Rev Mol Cell Biol 7(11):820–828. doi:http://www.nature.com/nrm/journal/v7/n11/suppinfo/nrm2041_S1.htmGoogle Scholar
  17. Kenakin T (2002) Drug efficacy at G protein-coupled receptors. Annu Rev Pharmacol Toxicol 42:349–379. doi:10.1146/annurev.pharmtox.42.091401.113012PubMedCrossRefGoogle Scholar
  18. Kerr R, Bartol TM, Kaminsky B, Dittrich M, Chang JCJ, Baden S, Sejnowski TJ, Stiles JR (2008) Fast Monte Carlo simulation methods for biological reaction-diffusion systems in solution and on surfaces. SIAM J Sci Comput 30(6):3126–3149PubMedCentralPubMedCrossRefGoogle Scholar
  19. Kim M, Huang T, Abel T, Blackwell KT (2010) Temporal sensitivity of protein kinase a activation in late-phase long term potentiation. PLoS Comput Biol 6(2):e1000691. doi:10.1371/journal.pcbi.1000691PubMedCentralPubMedCrossRefGoogle Scholar
  20. Kim B, Hawes SL, Gillani F, Wallace LJ, Blackwell KT (2013) Signaling pathways involved in striatal synaptic plasticity are sensitive to temporal pattern and exhibit spatial specificity. PLoS Comput Biol 9(3):e1002953. doi:10.1371/journal.pcbi.1002953PubMedCentralPubMedCrossRefGoogle Scholar
  21. Kinzer-Ursem TL, Linderman JJ (2007) Both ligand- and cell-specific parameters control ligand agonism in a kinetic model of g protein-coupled receptor signaling. PLoS Comput Biol 3(1):e6. doi:10.1371/journal.pcbi.0030006PubMedCentralPubMedCrossRefGoogle Scholar
  22. Linderman JJ (2009) Modeling of G-protein-coupled receptor signaling pathways. J Biol Chem 284(9):5427–5431PubMedCrossRefGoogle Scholar
  23. Magalhaes AC, Dunn H, Ferguson SS (2012) Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins. Br J Pharmacol 165(6):1717–1736. doi:10.1111/j.1476-5381.2011.01552.xPubMedCentralPubMedCrossRefGoogle Scholar
  24. Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118PubMedCrossRefGoogle Scholar
  25. Nakano T, Doi T, Yoshimoto J, Doya K (2010) A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity. PLoS Comput Biol 6(2):e1000670. doi:10.1371/journal.pcbi.1000670PubMedCentralPubMedCrossRefGoogle Scholar
  26. Neves SR, Iyengar R (2009) Models of spatially restricted biochemical reaction systems. J Biol Chem 284(9):5445–5449. doi:10.1074/jbc.R800058200PubMedCentralPubMedCrossRefGoogle Scholar
  27. Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R (2008) Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell 133(4):666–680. doi:10.1016/j.cell.2008.04.025PubMedCentralPubMedCrossRefGoogle Scholar
  28. Oliveira RF, Terrin A, Di Benedetto G, Cannon RC, Koh W, Kim M, Zaccolo M, Blackwell KT (2010) The role of type 4 phosphodiesterases in generating microdomains of cAMP: large scale stochastic simulations. PLoS One 5(7):e11725. doi:10.1371/journal.pone.0011725PubMedCentralPubMedCrossRefGoogle Scholar
  29. Oliveira RF, Kim M, Blackwell KT (2012) Subcellular location of PKA controls striatal plasticity: stochastic simulations in spiny dendrites. PLoS Comput Biol 8(2):e1002383. doi:10.1371/journal.pcbi.1002383PubMedCentralPubMedCrossRefGoogle Scholar
  30. Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993–996PubMedCrossRefGoogle Scholar
  31. Pargett M, Umulis DM (2013) Quantitative model analysis with diverse biological data: applications in developmental pattern formation. Methods 62(1):56–67. doi:10.1016/j.ymeth.2013.03.024PubMedCrossRefGoogle Scholar
  32. Romero G, von Zastrow M, Friedman PA (2011) Role of PDZ proteins in regulating trafficking, signaling, and function of GPCRs: means, motif, and opportunity. Adv Pharmacol 62:1557–8925Google Scholar
  33. Selent J, Kaczor AA (2011) Oligomerization of G protein-coupled receptors: computational methods. Curr Med Chem 18(30):4588–4605PubMedCrossRefGoogle Scholar
  34. Shenoy S, Lefkowitz RJ (2011) beta-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci 32(9):1873–3735. doi:10.1016/j.tips.2011.05.002CrossRefGoogle Scholar
  35. Simon AC, Loverdo C, Gaffuri A-L, Urbanski M, Ladarre D, Carrel D, Rivals I, Leterrier C, Benichou O, Dournaud P, Szabo B, Voituriez R, Lenkei Z (2013) Activation-dependent plasticity of polarized GPCR distribution on the neuronal surface. J Mol Cell Biol 5(4):250-265. doi:10.1093/jmcb/mjt014PubMedCrossRefGoogle Scholar
  36. Simpson LM, Taddese B, Wall ID, Reynolds CA (2010) Bioinformatics and molecular modelling approaches to GPCR oligomerization. Curr Opin Pharmacol 10(1):30–37. doi:10.1016/j.coph.2009.11.001PubMedCrossRefGoogle Scholar
  37. Stiles J, Bartol T (2001) Monte Carlo methods for simulating realistic synaptic microphysiology using MCell. In: De Schutter E (ed) Computational neuroscience: realistic modeling for experimentalists. CRC Press, Boca Raton, pp 87–127Google Scholar
  38. Vayttaden SJ, Bhalla US (2004) Developing complex signaling models using GENESIS/Kinetikit. Sci STKE 2004(219):pl4. doi:10.1126/stke.2192004pl4PubMedGoogle Scholar
  39. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Francesco VD, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji R-R, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang ZY, Wang A, Wang X, Wang J, Wei M-H, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu SC, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers Y-H, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigó R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang Y-H, Coyne M, Dahlke C, Mays AD, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (2001) The sequence of the human genome. Science 291(5507):1304–1351PubMedCrossRefGoogle Scholar
  40. Woolf PJ, Linderman JJ (2003) Self organization of membrane proteins via dimerization. Biophys Chem 104(1):217–227PubMedCrossRefGoogle Scholar
  41. Zheng Y, Rundell A (2006) Comparative study of parameter sensitivity analyses of the TCR-activated Erk-MAPK signalling pathway. Syst Biol 153(4):201–211CrossRefGoogle Scholar
  42. Zhong HL, Wade SM, Woolf PJ, Linderman JJ, Traynor JR, Neubig RR (2003) A spatial focusing model for G protein signals – regulator of G protein signaling (RGS) protein-mediated kinetic scaffolding. J Biol Chem 278(9):7278–7284PubMedCrossRefGoogle Scholar
  43. Zi Z, Zheng Y, Rundell AE, Klipp E (2008) SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool. BMC Bioinform 9:342. doi:10.1186/1471-2105-9-342CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Weldon School of Biomedical EngineeringPurdue UniversityWest LafayetteUSA