Christian Lohse
Experimental and mathematical analysis of cAMP nanodomains
Lohse, Christian; Bock, Andreas; Maiellaro, Isabella; Hannawacker, Annette; Schad, Lothar R.; Lohse, Martin J.; Bauer, Wolfgang R.
Authors
Andreas Bock
Dr ISABELLA MAIELLARO Isabella.Maiellaro@nottingham.ac.uk
ANNE MCLAREN FELLOWSHIP
Annette Hannawacker
Lothar R. Schad
Martin J. Lohse
Wolfgang R. Bauer
Contributors
Dr ISABELLA MAIELLARO Isabella.Maiellaro@nottingham.ac.uk
Work Package Leader
Abstract
In their role as second messengers, cyclic nucleotides such as cAMP have a variety of intracellular effects. These complex tasks demand a highly organized orchestration of spatially and temporally confined cAMP action which should be best achieved by compartmentalization of the latter. A great body of evidence suggests that cAMP compartments may be established and maintained by cAMP degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and biophysical details of how PDEs can orchestrate cAMP gradients are entirely unclear. In this paper, using fusion proteins of cAMP FRET-sensors and PDEs in living cells, we provide direct experimental evidence that the cAMP concentration in the vicinity of an individual PDE molecule is below the detection limit of our FRET sensors (<100nM). This cAMP gradient persists in crude cytosol preparations. We developed mathematical models based on diffusion-reaction equations which describe the creation of nanocompartments around a single PDE molecule and more complex spatial PDE arrangements. The analytically solvable equations derived here explicitly determine how the capability of a single PDE, or PDE complexes, to create a nanocompartment depend on the cAMP degradation rate, the diffusive mobility of cAMP, and geometrical and topological parameters. We apply these generic models to our experimental data and determine the diffusive mobility and degradation rate of cAMP. The results obtained for these parameters differ by far from data in literature for free soluble cAMP interacting with PDE. Hence, restricted cAMP diffusion in the vincinity of PDE is necessary to create cAMP nanocompartments in cells.
Citation
Lohse, C., Bock, A., Maiellaro, I., Hannawacker, A., Schad, L. R., Lohse, M. J., & Bauer, W. R. (2017). Experimental and mathematical analysis of cAMP nanodomains. PLoS ONE, 12(4), Article e0174856. https://doi.org/10.1371/journal.pone.0174856
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 1, 2017 |
Online Publication Date | Apr 13, 2017 |
Publication Date | Apr 13, 2017 |
Deposit Date | Apr 8, 2020 |
Publicly Available Date | May 20, 2020 |
Journal | PLOS ONE |
Electronic ISSN | 1932-6203 |
Publisher | Public Library of Science |
Peer Reviewed | Peer Reviewed |
Volume | 12 |
Issue | 4 |
Article Number | e0174856 |
DOI | https://doi.org/10.1371/journal.pone.0174856 |
Public URL | https://nottingham-repository.worktribe.com/output/4237301 |
Publisher URL | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174856 |
Files
Experimental and mathematical analysis
(2 Mb)
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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