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Cell Rep. 2019 Jun 25;27(13):4003-4012.e6. doi: 10.1016/j.celrep.2019.05.102.

SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation.

Author information

1
Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France.
2
CNRS, ESPCI-Paris, PSL Research University, Brain Plasticity Unit, UMR 8249, 10 rue Vauquelin, 75005 Paris, France.
3
INSERM, Sorbonne Université, Institut Pasteur, UMR_S 1120, 75012 Paris, France.
4
Laboratoire de Biochimie, Ecole Polytechnique, CNRS UMR 7654, 91128 Palaiseau, France.
5
CNRS, ESPCI-Paris, PSL Research University, Brain Plasticity Unit, UMR 8249, 10 rue Vauquelin, 75005 Paris, France; Université de Paris, Institute of Psychiatry and Neurosciences of Paris, INSERM U1266, 102-108 rue de la Santé, 75014 Paris, France.
6
Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France. Electronic address: xavier.nicol@inserm.fr.

Abstract

cGMP is critical to a variety of cellular processes, but the available tools to interfere with endogenous cGMP lack cellular and subcellular specificity. We introduce SponGee, a genetically encoded chelator of this cyclic nucleotide that enables in vitro and in vivo manipulations in single cells and in biochemically defined subcellular compartments. SponGee buffers physiological changes in cGMP concentration in various model systems while not affecting cAMP signals. We provide proof-of-concept strategies by using this tool to highlight the role of cGMP signaling in vivo and in discrete subcellular domains. SponGee enables the investigation of local cGMP signals in vivo and paves the way for therapeutic strategies that prevent downstream signaling activation.

KEYWORDS:

(T)hPDE5(VV); FRET; PKG; axon guidance; cGMP buffer; genetically encoded; lipid grafts; neuronal migration; single cell pharmacology; subcellular compartment

PMID:
31242429
DOI:
10.1016/j.celrep.2019.05.102
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