Mathematical model to study the nonlinear influence of Dyrk1A in actin polymerization

Abstract

Event Abstract Back to Event Mathematical model to study the nonlinear influence of Dyrk1A in actin polymerization German A. Patterson1* and Mara Dierssen1 1 Center for Genomic Regulation, Spain Dyrk1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. It is believed that Dyrk1A plays a significant role in signaling pathways regulating cell proliferation and may be involved in neuron development. On the one hand, it has been reported that overexpression of Dyrk1A is sufficient to produce the dendritic alterations, in particular, it was shown that changes in Dyrk1A gene dosage strongly alter the dendritic arborization processes characterized by a reduction of neurite outgrowth [Martinez de Legran et al., 2012]. On the other hand, it was found that cells in Dyrk1A+/- mouse, a model lacking one copy of Dyrk1A, were less branched and less spinous than WT. This results suggest that Dyrk1A is affecting cellular pathways involved in neural development in a way that dosage changes lead to similar alteration regardless the direction of this change [Benavides-Piccione et al., 2005]. Here, we present a simple mathematical model that may explain both alterations observed in Dyrk1A+/- and Ts65Dn. It is based on a model proposed by Park et al., which describes a regulatory mechanism for Neural Wiskott–Aldrich syndrome protein (N-WASP) activity through Dyrk1A phosphorylation and how it regulates the actin filament assembly [Park et al., 2011]. In this work, we present a full characterization of the behavior of the system as a function of different set of parameters. We study how Dyrk1A may affect the dynamics of the system and how Dyrk1A dosage may regulate the actin polymerization. We believe that these findings may shed same light on how Dyrk1A affects cellular processes such as morphogenesis and neuronal differentiation. References R. Benavides-Piccione, M. Dierssen, I. Ballesteros-Yáñez, M. Martínez de Lagrán, M.L. Arbonés, V. Fotaki, J. DeFelipe, G.N. Elston, Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+/− mouse, Neurobiology of Disease, Volume 20, Issue 1, October 2005, Pages 115-122, ISSN 0969-9961, doi:10.1016/j.nbd.2005.02.004. M. Martinez de Lagran, R. Benavides-Piccione, I. Ballesteros-Yañez, M. Calvo, M. Morales, C. Fillat, J. DeFelipe, G. J. A. Ramakers, and M. Dierssen, Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons, Cereb. Cortex (2012) 22 (12): 2867-2877, doi:10.1093/cercor/bhr362 Joongkyu Park, Jee Young Sung, Joohyun Park, Woo-Joo Song, Sunghoe Chang, and Kwang Chul Chung, Dyrk1A negatively regulates the actin cytoskeleton through threonine phosphorylation of N-WASP, J Cell Sci 2012 125:67-80, doi:10.1242/jcs.086124 Keywords: Cellular Pathway Analysis and Simulation, Morphogenesis, actin polymerization, DYRK1A, NWASP Conference: B·DEBATE | A Dialogue with the Cerebral Cortex: Cortical Function and Interfacing (Workshop), Barcelona, Spain, 29 Apr - 30 Apr, 2015. Presentation Type: Poster Presentation Topic: SESSION 1: Cortical Function and Computations Citation: Patterson GA and Dierssen M (2015). Mathematical model to study the nonlinear influence of Dyrk1A in actin polymerization. Front. Syst. Neurosci. Conference Abstract: B·DEBATE | A Dialogue with the Cerebral Cortex: Cortical Function and Interfacing (Workshop). doi: 10.3389/conf.fnsys.2015.06.00006 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: 22 Apr 2015; Published Online: 06 May 2015. * Correspondence: Dr. German A Patterson, Center for Genomic Regulation, Barcelona, Spain, german.patterson@crg.eu 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 German A Patterson Mara Dierssen Google German A Patterson Mara Dierssen Google Scholar German A Patterson Mara Dierssen PubMed German A Patterson Mara Dierssen 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.