Skip to main content

Research Repository

Advanced Search

Experimental and mathematical analysis of cAMP nanodomains

Lohse, Christian; Bock, Andreas; Maiellaro, Isabella; Hannawacker, Annette; Schad, Lothar R.; Lohse, Martin J.; Bauer, Wolfgang R.

Experimental and mathematical analysis of cAMP nanodomains Thumbnail


Authors

Christian Lohse

Andreas Bock

Annette Hannawacker

Lothar R. Schad

Martin J. Lohse

Wolfgang R. Bauer



Contributors

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





You might also like



Downloadable Citations