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A process model of Rho GTP-binding proteins. (English) Zbl 1173.68040
Summary: Rho GTP-binding proteins play a key role as molecular switches in many cellular activities. In response to extracellular stimuli and with the help of regulators (GEF, GAP, Effector, GDI), these proteins serve as switches that interact with their environment in a complex manner. Based on the structure of a published Ordinary Differential Equations (ODE) model, we first present a generic process model for the Rho GTP-binding proteins, and compare it with the ODE model. We then extend the basic model to include the behaviour of the GDI regulators and explore the parameter space for the extended model with respect to biological data from the literature. We discuss the challenges this extension brings and the directions of further research. In particular, we present techniques for modular representation and refinement of process models, where, for example, different Rho proteins with different rates for regulator interactions can be given as instances of the same parametric model.

68Q85 Models and methods for concurrent and distributed computing (process algebras, bisimulation, transition nets, etc.)
92B05 General biology and biomathematics
92C37 Cell biology
Full Text: DOI
[1] Alberts, Bruce; Johnson, Alexander; Walter, Peter; Lewis, Julian; Raff, Martin; Roberts, Keith, Molecular biology of the cell, (2008), Garland Science
[2] Blossey, Ralf; Cardelli, Luca; Phillips, Andrew, A compositional approach to the stochastic dynamics of gene networks, Transactions in computational systems biology, 3939, 99-122, (2006) · Zbl 1179.92021
[3] Bustelo, Xose R.; Sauzeau, Vincent; Berenjeno, Inmaculada M., GTP-binding proteins of the rho/rac family: regulation, effectors and function in vivo, Bioessays, 29, 356-370, (2007)
[4] Cardelli, Luca, On process rate semantics, Theoretical computer science, 391, 190-215, (2008) · Zbl 1133.68054
[5] Cardelli, Luca; Caron, Emmanuelle; Gardner, Philippa; Kahramanoğulları, Ozan; Phillips, Andrew, A process model of actin polymerisation, (), 127-144 · Zbl 1283.92047
[6] Chimini, Giovanni; Chavrier, Philippe, Function of rho family proteins in actin dynamics during phagocytosis and engulfment, Nature cell biology, 2, 191-196, (2000)
[7] DerMardirossian, Céline; Bokoch, Gary M., GDIs: central regulatory molecules in rho gtpase activation, TRENDS in cell biology, 15, 7, 356-363, (2005)
[8] Dovas, Athanassios; Couchman, John R., Rhogdi: multiple functions in the regulation of rho family gtpase activities, Biochemistry journal, 390, 1-9, (2005)
[9] Dransart, Estelle; Olofsson, Birgitta; Cherfils, Jacqueline, Rhogdis revisted: novel roles in rho regulation, Traffic, 6, 957-966, (2005)
[10] Etienne-Manneville, Sandrine; Hall, Alan, Rho gtpases in cell biology, Nature, 420, 629-635, (2002)
[11] Garcia-Garcia, Erick; Rosales, Carlos, Signal transduction during fc receptor-mediated phagocytosis, Journal of leukocyte biology, 72, 1092-1108, (2002)
[12] Gillespie, Daniel T., Exact stochastic simulation of coupled chemical reactions, The journal of physical chemistry, 81(25), 2340-2361, (1977)
[13] Goryachev, Andrew B.; Pokhilko, Alexandra V., Computational model explains high activity and rapid cycling of rho gtpases within protein complexes, PLOS computational biology, 2, 1511-1521, (2006), For the license terms of the figures adapted from this work, see http://creativecommons.org/licenses/by/2.5/
[14] Goryachev, Andrew B.; Pokhilko, Alexandra V., Dynamics of cdc42 network embodies a Turing-type mechanism of yeast cell polarity, FEBS letters, 582, 10, 1437-1443, (2008)
[15] Hall, A.B.; Gakidis, M. A.; Glogauer, M; Wilsbacher, J.L.; Gao, S; Swat, W.; Brugge, J.S., Requirements for vav guanine nucleotide exchange factors and rho gtpases in fc\(\gamma\)R- and complement-mediated phagocytosis, Immunity, 24, 305-316, (2006)
[16] Jaffe, Aron B.; Hall, Alan, Rho gtpases: biochemistry and biology, Annual review of cell and developmental biology, 21, 247-269, (2005)
[17] Lecca, P.; Priami, C., Cell cycle control in eukaryotes: A biospi model, ()
[18] Olofsson, B., Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling, Cell signal., 11, 8, 545-554, (1999)
[19] Patel, J.C.; Hall, A.; Caron, E., Vav regulates activation of rac but not cdc42 during fc\(\gamma\)R-mediated phagocytosis, Molecular biology of the cell, 13, 1215-1226, (2002)
[20] Phillips, A.; Cardelli, L.; Castagna, G., A graphical representation for biological processes in the stochastic pi-calculus, Transactions in computational systems biology, 4230, 123-152, (2006)
[21] Phillips, Andrew; Cardelli, Luca, Efficient, correct simulation of biological processes in the stochastic pi-calculus, (), 184-199
[22] Platko, J.V.; Leonard, D.A.; Adra, C.N.; Shaw, R.J.; Cerione, R.A.; Lim, B., A single residue can modify target-binding affinity and activity of the functional domain of the rho-subfamily GDP dissociation inhibitors, Proceedings of the national Academy of sciences of the united states of America, 92, 7, 2974-2978, (1995)
[23] Pozo, Miguel Angel Del; Kiosses, William B.; Alderson, Nazilla B.; Meller, Nahum; Hahn, Klaus M.; Schwartz, Martin Alexander, Integrins regulate GTP-rac localized effector interactions through dissociation of rho-GDI, Nature cell biology, 4, 232-239, (2002)
[24] Priami, C.; Regev, A.; Shapiro, E.; Silverman, W., Application of a stochastic name-passing calculus to representation and simulation of molecular processes, Information processing letters, 80, 25-31, (2001) · Zbl 0997.92018
[25] Scheffzek, Klaus; Stephan, Ilona; Jensen, Ole N.; Illenberger, Daria; Gierschik, Peter, The rac-rhogdi complex and the structural basis for the regulation of rho proteins by rhogdi, Nature structural biology, 7, 122-126, (2000)
[26] Swanson, Joel A.; Hoppe, Adam D., Cdc42, rac1, and rac2 display distinct patterns of activation during phagocytosis, Molecular biology of the cell, 15(8), 3509-3519, (2004)
[27] Wolkenhauer, O.; Ullah, M.; Kolch, W.; K.H., Cho, Modeling and simulation of intracellular dynamics: choosing an appropriate framework, IEEE transactions in nanobioscience, 3, 200-207, (2004)
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