Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation

Valeyev, Najil, Kim, Jung-Su, Heslop-Harrison, Pat, Postlethwaite, Ian, Kotov, Nikolay and Bates, Declan (2009) Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation. Molecular BioSystems, 5 (6). pp. 612-628. ISSN 1742-206X

[img]
Preview
PDF (Article)
b822074c.pdf - Published Version

Download (1MB) | Preview
Official URL: http://dx.doi.org/10.1039/B822074C

Abstract

Under conditions of starvation, Dictyostelium cells begin a programme of development during which they aggregate to form a multicellular structure by chemotaxis, guided by propagating waves of cyclic AMP that are relayed robustly from cell to cell. In this paper, we develop and analyse a new model for the intracellular and extracellular cAMP dependent processes that regulate Dictyostelium migration. The model allows, for the first time, a quantitative analysis of the dynamic interactions between calcium, IP(3) and G protein-dependent modules that are shown to be key to the generation of robust cAMP oscillations in Dictyostelium cells. The model provides a mechanistic explanation for the transient increase in cytosolic free Ca(2+) concentration seen in recent experiments with the application of the calmodulin inhibitor calmidazolium (R24571) to Dictyostelium cells, and also allows elucidation of the effects of varying both the conductivity of stretch-activated channels and the concentration of external phosphodiesterase on the oscillatory regime of an individual cell. A rigorous analysis of the robustness of the new model shows that interactions between the different modules significantly reduce the sensitivity of the resulting cAMP oscillations to variations in the kinetics of different Dictyostelium cells, an essential requirement for the generation of the spatially and temporally synchronised chemoattractant cAMP waves that guide Dictyostelium aggregation.

Item Type: Article
Subjects: H600 Electronic and Electrical Engineering
Department: Faculties > Engineering and Environment > Mathematics, Physics and Electrical Engineering
Depositing User: Sarah Howells
Date Deposited: 15 Oct 2012 17:02
Last Modified: 16 May 2017 08:47
URI: http://nrl.northumbria.ac.uk/id/eprint/9682

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics


Policies: NRL Policies | NRL University Deposit Policy | NRL Deposit Licence