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Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels

Valeyev, Najl V., Heslop-Harrison, Pat, Postlethwaite, Ian, Gizatullina, Antonina N., Kotov, Nikolay V., Bates, Declan G. (2009) Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels. Molecular BioSystems, 5 (1). pp. 43-51. ISSN 1742-206X. (doi:10.1039/b807993e) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:35732)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL
http://dx.doi.org/10.1039/b807993e

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.

Item Type: Article
DOI/Identification number: 10.1039/b807993e
Subjects: T Technology
Divisions: Divisions > Division of Computing, Engineering and Mathematical Sciences > School of Engineering and Digital Arts
Depositing User: Tina Thompson
Date Deposited: 28 Oct 2013 16:39 UTC
Last Modified: 16 Nov 2021 10:12 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/35732 (The current URI for this page, for reference purposes)
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