Anchoring proteins and phosphodiesterases: A stochastic reaction diffusion simulation of cAMP microdomains

Abstract

Event Abstract Back to Event Anchoring proteins and phosphodiesterases: A stochastic reaction diffusion simulation of cAMP microdomains Rodrigo F. Oliveira1*, Myungsook Kim2, Kim T. Blackwell2 and Manuela Zaccolo3 1 George Mason University, United States 2 Krasnow Institute for Advanced Studies, United States 3 Faculty of Biomedical & Life Sciences, United Kingdom Cyclic AMP (cAMP) is an important second messenger molecule responsible for regulation of many aspects of cell function such as long term synaptic plasticity in neurons. Though cAMP diffuses throughout a cell relatively rapidly, specificity in cAMP activation of downstream targets is achieved by mechanisms which produce spatial gradients and microdomains of cAMP concentration. Recent experiments suggest that compartmentalized phosphodiesterases (PDE) act as localized 'sinks', producing gradients of cAMP. To test the role of compartmentalized PDEs in producing spatial gradients, we develop a computational model of cAMP production, PKA activation and compartmentalized PDE activity using the Rapid, Approximate, Stochastic reaction-diffusion (RASrd) algorithm. In the model cell, adenylyl cyclase, PKA and PDE4B are anchored to the submembrane compartment, PKA and PDE4D are anchored in the cytosol, and cAMP freely diffuses. To precisely compare simulated results with FRET imaging data, we calculate the theoretical FRET signal from simulated concentrations of cAMP bound and free Epac or PKA, and include contamination terms due to overlap of emission and excitation spectra. The model reproduces the cAMP gradient (both free cAMP and the calculated FRET signal) between submembrane and cytosolic compartments. Simulations results with reduced PDE activity and different cAMP diffusion constants also show the dependence of the gradient on both PDE4D cytosoloic anchoring and cAMP diffusion suggesting that reduced cAMP diffusivity may also play a role in compartmentalization. Furthermore, our simulations demonstrate the utility of the new stochastic reaction-diffusion algorithm for exploring signaling pathways in spatially complex structures such as neurons. Conference: Neuroinformatics 2008, Stockholm, Sweden, 7 Sep - 9 Sep, 2008. Presentation Type: Poster Presentation Topic: Computational Neuroscience Citation: Oliveira RF, Kim M, Blackwell KT and Zaccolo M (2008). Anchoring proteins and phosphodiesterases: A stochastic reaction diffusion simulation of cAMP microdomains. Front. Neuroinform. Conference Abstract: Neuroinformatics 2008. doi: 10.3389/conf.neuro.11.2008.01.048 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jul 2008; Published Online: 28 Jul 2008. * Correspondence: Rodrigo F Oliveira, George Mason University, Fairfax, United States, roliveir@gmu.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rodrigo F Oliveira Myungsook Kim Kim T Blackwell Manuela Zaccolo Google Rodrigo F Oliveira Myungsook Kim Kim T Blackwell Manuela Zaccolo Google Scholar Rodrigo F Oliveira Myungsook Kim Kim T Blackwell Manuela Zaccolo PubMed Rodrigo F Oliveira Myungsook Kim Kim T Blackwell Manuela Zaccolo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.