Abstract:
:Cyclic adenosine monophosphate and cyclic guanosine monophosphate are universal intracellular messengers whose concentrations are regulated by molecular networks comprised of different isoforms of the synthases adenylate cyclase or guanylate cyclase and the phosphodiesterases which degrade these compounds. In this paper, we employ a systems biology approach to develop mathematical models of these networks that, for the first time, take into account the different biochemical properties of the isoforms involved. To investigate the mechanisms underlying the joint regulation of cAMP and cGMP, we apply our models to analyse the regulation of cilia beat frequency in Paramecium by Ca(2+). Based on our analysis of these models, we propose that the diversity of isoform combinations that occurs in living cells provides an explanation for the huge variety of intracellular processes that are dependent on these networks. The inclusion of both G-protein receptor and Ca(2+)-dependent regulation of AC in our models allows us to propose a new explanation for the switching properties of G-protein subunits involved in nucleotide regulation. Analysis of the models suggests that, depending on whether the G-protein subunit is bound to AC, Ca(2+) can either activate or inhibit AC in a concentration-dependent manner. The resulting analysis provides an explanation for previous experimental results that showed that alterations in Ca(2+) concentrations can either increase or decrease cilia beat frequency over particular Ca(2+) concentration ranges.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Valeyev NV,Heslop-Harrison P,Postlethwaite I,Gizatullina AN,Kotov NV,Bates DGdoi
10.1039/b807993esubject
Has Abstractpub_date
2009-01-01 00:00:00pages
43-51issue
1eissn
1742-206Xissn
1742-2051journal_volume
5pub_type
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