The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 10 of 322
Back to Result List

Experimental and mathematical analysis of cAMP nanodomains

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170972
  • 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 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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Christian Lohse, Andreas Bock, Isabella Maiellaro, Annette Hannawacker, Lothar R. Schad, Martin J. Lohse, Wolfgang R. Bauer
URN:urn:nbn:de:bvb:20-opus-170972
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2017
Volume:12
Issue:4
Pagenumber:e0174856
Source:PLoS ONE 12(4):e0174856 (2017). DOI: 10.1371/journal.pone.0174856
DOI:https://doi.org/10.1371/journal.pone.0174856
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28406920
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:absorption; adenylyl cyclase signaling cascade; cell fusion; cyclic nucleotides such as cyclic adenosine monophosphate; cytosol; fluorescence resonance energy transfer; isoproterenol; radii; yellow fluorescent protein
Release Date:2019/10/14
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International