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

Oriol Ros¹, Yvrick Zagar¹, Solène Ribes¹

¹Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France.

|June 27, 2019

Summary

Researchers developed SponGee, a novel tool for precisely controlling cyclic guanosine monophosphate (cGMP) levels within cells. This genetically encoded chelator allows targeted manipulation of cGMP signaling in specific cellular locations, advancing biological research and therapeutic development.

Keywords:

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

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Area of Science:

Molecular Biology
Cellular Signaling
Biochemistry

Background:

Cyclic guanosine monophosphate (cGMP) is essential for numerous cellular functions.
Existing methods for modulating cGMP lack precise cellular and subcellular control.
Targeted manipulation of cGMP is crucial for understanding its diverse roles.

Purpose of the Study:

To introduce SponGee, a genetically encoded chelator for cyclic nucleotide manipulation.
To demonstrate SponGee's utility for precise in vitro and in vivo control of cGMP.
To explore the role of localized cGMP signaling in cellular processes.

Main Methods:

Development of SponGee, a genetically encoded cGMP chelator.
Application of SponGee in various model systems for buffering cGMP changes.
Validation of SponGee's specificity, ensuring no interference with cAMP signals.
Proof-of-concept experiments demonstrating in vivo and subcellular cGMP manipulation.

Main Results:

SponGee successfully buffers physiological changes in cGMP concentration across different model systems.
The tool exhibits specificity, not affecting cyclic adenosine monophosphate (cAMP) signaling.
Demonstrated the ability to investigate cGMP signaling in vivo and within specific subcellular compartments.
Provided evidence for the role of localized cGMP in cellular functions.

Conclusions:

SponGee offers unprecedented precision for manipulating cGMP signaling at cellular and subcellular levels.
This tool facilitates the investigation of localized cGMP dynamics in vivo.
SponGee holds potential for developing targeted therapeutic strategies by modulating downstream signaling pathways.