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

摘要

cGMP is critical to a variety of cellular processes, butthe available tools to interfere with endogenouscGMP lack cellular and subcellular specificity. Weintroduce SponGee, a genetically encoded chelatorof this cyclic nucleotide that enables in vitro andin vivo manipulations in single cells and in biochemicallydefined subcellular compartments. SponGeebuffers physiological changes in cGMP concentrationin various model systems while not affectingcAMP signals. We provide proof-of-concept strategiesby using this tool to highlight the role ofcGMP signaling in vivo and in discrete subcellulardomains. SponGee enables the investigation of localcGMP signals in vivo and paves the way for therapeuticstrategies that prevent downstream signalingactivation.