PDE4 Control on cAMP/PKA Compartmentation Revealed by Biosensor Imaging in Neurons

P. Vincent; L.R. V. Castro; N. Gervasi; E. Guiot; M. Brito; D. Paupardin-Tritsch

doi:10.1055/s-0032-1311631

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2012; 44(10): 786-789
DOI: 10.1055/s-0032-1311631

Original Basic

PDE4 Control on cAMP/PKA Compartmentation Revealed by Biosensor Imaging in Neurons

Authors

P. Vincent

¹Centre National de la Recherche Scientifique, Unité Mixe de Recherche UMR7102, Paris, France

²Université Pierre et Marie Curie, UPMC, Unité Mixe de Recherche UMR7102, Paris, France
L.R. V. Castro

¹Centre National de la Recherche Scientifique, Unité Mixe de Recherche UMR7102, Paris, France

²Université Pierre et Marie Curie, UPMC, Unité Mixe de Recherche UMR7102, Paris, France
N. Gervasi

¹Centre National de la Recherche Scientifique, Unité Mixe de Recherche UMR7102, Paris, France

²Université Pierre et Marie Curie, UPMC, Unité Mixe de Recherche UMR7102, Paris, France

³Current Address: Inserm UMR-S 839, Institut du Fer à Moulin, Paris, France
E. Guiot

¹Centre National de la Recherche Scientifique, Unité Mixe de Recherche UMR7102, Paris, France

²Université Pierre et Marie Curie, UPMC, Unité Mixe de Recherche UMR7102, Paris, France
M. Brito

¹Centre National de la Recherche Scientifique, Unité Mixe de Recherche UMR7102, Paris, France

²Université Pierre et Marie Curie, UPMC, Unité Mixe de Recherche UMR7102, Paris, France
D. Paupardin-Tritsch

¹Centre National de la Recherche Scientifique, Unité Mixe de Recherche UMR7102, Paris, France

²Université Pierre et Marie Curie, UPMC, Unité Mixe de Recherche UMR7102, Paris, France

Abstract

Electrophysiological recordings (using the slow-AHP potassium current) together with novel biosensor imaging methods (with AKAR and Epac sensors) were used in preparations of rodent brain slices to record PKA activation in real time and in individual neurons. The experiments revealed the propagation of the PKA signal from the membrane to the cytosol and eventually to the nucleus. The experiments show how the geometry of the neurons combined with phosphodiesterase activities (mostly rolipram-sensitive PDE4) contributes to a functional compartmentation of the cAMP in subcellular domains.

Key words

imaging - phosphodiesterase - protein kinase - cyclic AMP - neuron - cortex

Full Text

References

References
1 Tasken K, Aandahl EM. Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 2004; 84: 137-167
2 Wong W, Scott JD. AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 2004; 5: 959-970
3 Willoughby D, Cooper DM. Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains. Physiol Rev 2007; 87: 965-1010
4 McCahill AC, Huston E, Li X, Houslay MD. PDE4 associates with different scaffolding proteins: modulating interactions as treatment for certain diseases. Handb Exp Pharmacol 2008; 125-166
5 Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell 2008; 133: 666-680
6 Zhang J, Campbell RE, Ting AY, Tsien RY. Creating new fluorescent probes for cell biology. Nat Rev Mol Cell Biol 2002; 3: 906-918
7 Nikolaev VO, Bunemann M, Hein L, Hannawacker A, Lohse MJ. Novel single chain cAMP sensors for receptor-induced signal propagation. J Biol Chem 2004; 279: 37215-37218
8 Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang H, Ke H, Nikolaev VO, Jaffe LA. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development 2009; 136: 1869-1878
9 Zhang J, Hupfeld CJ, Taylor SS, Olefsky JM, Tsien RY. Insulin disrupts beta-adrenergic signalling to protein kinase A in adipocytes. Nature 2005; 437: 569-573
10 Allen MD, Zhang J. Subcellular dynamics of protein kinase A activity visualized by FRET-based reporters. Biochem Biophys Res Commun 2006; 348: 716-721
11 Ehrengruber MU, Lundstrom K, Schweitzer C, Heuss C, Schlesinger S, Gahwiler BH. Recombinant Semliki Forest virus and Sindbis virus efficiently infect neurons in hippocampal slice cultures. Proc Natl Acad Sci USA 1999; 96: 7041-7046
12 Gervasi N, Hepp R, Tricoire L, Zhang J, Lambolez B, Paupardin-Tritsch D, Vincent P. Dynamics of protein kinase A signaling at the membrane, in the cytosol, and in the nucleus of neurons in mouse brain slices. J Neurosci 2007; 27: 2744-2750
13 O’Donnell JM, Zhang HT. Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4). Trends Pharmacol Sci 2004; 25: 158-163
14 Castro LR, Gervasi N, Guiot E, Cavellini L, Nikolaev VO, Paupardin-Tritsch D, Vincent P. Type 4 phosphodiesterase plays different integrating roles in different cellular domains in pyramidal cortical neurons. J Neurosci 2010; 30: 6143-6151
15 Houslay MD, Schafer P, Zhang KY. Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 2005; 10: 1503-1519
16 Millar JK, Pickard BS, Mackie S, James R, Christie S, Buchanan SR, Malloy MP, Chubb JE, Huston E, Baillie GS, Thomson PA, Hill EV, Brandon NJ, Rain JC, Camargo LM, Whiting PJ, Houslay MD, Blackwood DH, Muir WJ, Porteous DJ. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 2005; 310: 1187-1191
17 Clapcote SJ, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, Lerch JP, Trimble K, Uchiyama M, Sakuraba Y, Kaneda H, Shiroishi T, Houslay MD, Henkelman RM, Sled JG, Gondo Y, Porteous DJ, Roder JC. Behavioral phenotypes of disc1 missense mutations in mice. Neuron 2007; 54: 387-402