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Metabotropic Receptors (G Protein-Coupled Receptors)

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Encyclopedia of Computational Neuroscience

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Synonyms

7TM receptors; Computational modeling; Dynamic models; G protein-linked receptors; Heptahelical receptors; Mathematical modeling; Serpentine receptors; Seven-transmembrane domain receptors; Spatial modeling; Systems biology; Time-dependent modeling

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...

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References

  • 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 519–542

    Chapter  Google Scholar 

  • Andrews SS, Addy NJ, Brent R, Arkin AP (2010) Detailed simulations of cell biology with Smoldyn 2.1. PLoS Comput Biol 6(3):e1000705

    Article  PubMed Central  PubMed  Google Scholar 

  • 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_249

    PubMed  Google Scholar 

  • 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.104.040469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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.104.040501

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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.2013.05.008

    Google Scholar 

  • 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_5

    Article  CAS  Google Scholar 

  • Brinkerhoff CJ, Woolf PJ, Linderman JJ (2004) Monte Carlo simulations of receptor dynamics: insights into cell signaling. J Mol Histol 35(7):667–677

    PubMed  Google Scholar 

  • 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.1204

    Article  CAS  PubMed  Google Scholar 

  • 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/b978-0-12-388403-9.00008-4

    Article  Google Scholar 

  • 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 

  • 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.0020176

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.x

    Article  CAS  PubMed  Google Scholar 

  • 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.2011.03.010

    Article  CAS  PubMed  Google Scholar 

  • 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)01636-9

    Article  CAS  PubMed  Google Scholar 

  • 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.htm

    Google Scholar 

  • Kenakin T (2002) Drug efficacy at G protein-coupled receptors. Annu Rev Pharmacol Toxicol 42:349–379. doi:10.1146/annurev.pharmtox.42.091401.113012

    Article  CAS  PubMed  Google Scholar 

  • 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):3126–3149

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.1000691

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.1002953

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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.0030006

    Article  PubMed Central  PubMed  Google Scholar 

  • Linderman JJ (2009) Modeling of G-protein-coupled receptor signaling pathways. J Biol Chem 284(9):5427–5431

    Article  CAS  PubMed  Google Scholar 

  • 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.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118

    Article  CAS  PubMed  Google Scholar 

  • 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.1000670

    Article  PubMed Central  PubMed  Google Scholar 

  • Neves SR, Iyengar R (2009) Models of spatially restricted biochemical reaction systems. J Biol Chem 284(9):5445–5449. doi:10.1074/jbc.R800058200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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.2008.04.025

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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.0011725

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.1002383

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993–996

    Article  CAS  PubMed  Google Scholar 

  • 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.2013.03.024

    Article  CAS  PubMed  Google Scholar 

  • 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 62:1557–8925

    Google Scholar 

  • Selent J, Kaczor AA (2011) Oligomerization of G protein-coupled receptors: computational methods. Curr Med Chem 18(30):4588–4605

    Article  CAS  PubMed  Google Scholar 

  • 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.2011.05.002

    Article  Google Scholar 

  • 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/mjt014

    Article  CAS  PubMed  Google Scholar 

  • 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.2009.11.001

    Article  CAS  PubMed  Google Scholar 

  • 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 87–127

    Google Scholar 

  • Vayttaden SJ, Bhalla US (2004) Developing complex signaling models using GENESIS/Kinetikit. Sci STKE 2004(219):pl4. doi:10.1126/stke.2192004pl4

    PubMed  Google Scholar 

  • 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):1304–1351

    Article  CAS  PubMed  Google Scholar 

  • Woolf PJ, Linderman JJ (2003) Self organization of membrane proteins via dimerization. Biophys Chem 104(1):217–227

    Article  CAS  PubMed  Google Scholar 

  • Zheng Y, Rundell A (2006) Comparative study of parameter sensitivity analyses of the TCR-activated Erk-MAPK signalling pathway. Syst Biol 153(4):201–211

    Article  Google Scholar 

  • 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):7278–7284

    Article  CAS  PubMed  Google Scholar 

  • 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:10.1186/1471-2105-9-342

    Article  Google Scholar 

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Authors and Affiliations

  1. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA

    Tamara Kinzer-Ursem Ph.D.

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  1. Tamara Kinzer-Ursem Ph.D.
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Correspondence to Tamara Kinzer-Ursem Ph.D. .

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Editors and Affiliations

  1. Atlanta, Georgia, USA

    Dieter Jaeger

  2. Department of Biomedical Engineering, Florida International University, Miami, Florida, USA

    Ranu Jung

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Kinzer-Ursem, T. (2014). Metabotropic Receptors (G Protein-Coupled Receptors). In: Jaeger, D., Jung, R. (eds) Encyclopedia of Computational Neuroscience. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7320-6_190-2

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

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Chapter history

  1. Latest

    Metabotropic Receptors (G Protein-Coupled Receptors)
    Published:
    06 May 2014

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

  2. Original

    GPCR Models in Neuroscience in Molecular and Diffusion Modeling
    Published:
    15 March 2014

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

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