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

Summary: 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...

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Main Authors: Oriol Ros, Yvrick Zagar, Solène Ribes, Sarah Baudet, Karine Loulier, Sandrine Couvet, Delphine Ladarre, Alain Aghaie, Alice Louail, Christine Petit, Yves Mechulam, Zsolt Lenkei, Xavier Nicol
Format: Article
Language:English
Published: Elsevier 2019-06-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719307417
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author Oriol Ros
Yvrick Zagar
Solène Ribes
Sarah Baudet
Karine Loulier
Sandrine Couvet
Delphine Ladarre
Alain Aghaie
Alice Louail
Christine Petit
Yves Mechulam
Zsolt Lenkei
Xavier Nicol
author_facet Oriol Ros
Yvrick Zagar
Solène Ribes
Sarah Baudet
Karine Loulier
Sandrine Couvet
Delphine Ladarre
Alain Aghaie
Alice Louail
Christine Petit
Yves Mechulam
Zsolt Lenkei
Xavier Nicol
author_sort Oriol Ros
collection DOAJ
description Summary: 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. : Ros et al. developed SponGee, a genetically encoded cGMP chelator that enables the manipulation of this second messenger in single cells with subcellular specificity. SponGee alters the migration of developing cortical neurons in vivo. Lipid raft targeting of SponGee prevents axon repulsion, in contrast to exclusion from this subcellular compartment. Keywords: cGMP buffer, subcellular compartment, single cell pharmacology, axon guidance, neuronal migration, lipid grafts, genetically encoded, FRET, ThPDE5VV, PKG
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spelling doaj.art-85acaec3e5044d8f9d3a2f5fa1a89f362022-12-22T00:27:36ZengElsevierCell Reports2211-12472019-06-01271340034012.e6SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP ManipulationOriol Ros0Yvrick Zagar1Solène Ribes2Sarah Baudet3Karine Loulier4Sandrine Couvet5Delphine Ladarre6Alain Aghaie7Alice Louail8Christine Petit9Yves Mechulam10Zsolt Lenkei11Xavier Nicol12Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceCNRS, ESPCI-Paris, PSL Research University, Brain Plasticity Unit, UMR 8249, 10 rue Vauquelin, 75005 Paris, FranceINSERM, Sorbonne Université, Institut Pasteur, UMR_S 1120, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceINSERM, Sorbonne Université, Institut Pasteur, UMR_S 1120, 75012 Paris, FranceLaboratoire de Biochimie, Ecole Polytechnique, CNRS UMR 7654, 91128 Palaiseau, FranceCNRS, 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, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France; Corresponding authorSummary: 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. : Ros et al. developed SponGee, a genetically encoded cGMP chelator that enables the manipulation of this second messenger in single cells with subcellular specificity. SponGee alters the migration of developing cortical neurons in vivo. Lipid raft targeting of SponGee prevents axon repulsion, in contrast to exclusion from this subcellular compartment. Keywords: cGMP buffer, subcellular compartment, single cell pharmacology, axon guidance, neuronal migration, lipid grafts, genetically encoded, FRET, ThPDE5VV, PKGhttp://www.sciencedirect.com/science/article/pii/S2211124719307417
spellingShingle Oriol Ros
Yvrick Zagar
Solène Ribes
Sarah Baudet
Karine Loulier
Sandrine Couvet
Delphine Ladarre
Alain Aghaie
Alice Louail
Christine Petit
Yves Mechulam
Zsolt Lenkei
Xavier Nicol
SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation
Cell Reports
title SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation
title_full SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation
title_fullStr SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation
title_full_unstemmed SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation
title_short SponGee: A Genetic Tool for Subcellular and Cell-Specific cGMP Manipulation
title_sort spongee a genetic tool for subcellular and cell specific cgmp manipulation
url http://www.sciencedirect.com/science/article/pii/S2211124719307417
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