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

Najil Valeyev, Jung-Su Kim, Pat Heslop-Harrison, Ian Postlethwaite, Nikolay Kotov, Declan Bates

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)
    3 Downloads (Pure)

    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.
    Original languageEnglish
    Pages (from-to)612-628
    JournalMolecular BioSystems
    Volume5
    Issue number6
    DOIs
    Publication statusPublished - Apr 2009

    Fingerprint Dive into the research topics of 'Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation'. Together they form a unique fingerprint.

    Cite this