SpiCee: A Genetic Tool for Subcellular and Cell-Specific Calcium Manipulation

Calcium is a second messenger crucial to a myriad of cellular processes ranging from regulation of metabolism and cell survival to vesicle release and motility. Current strategies to directly manipulate endogenous calcium signals lack cellular and subcellular specificity. We introduce SpiCee, a versatile and genetically encoded chelator combining low- and high-affinity sites for calcium. This scavenger enables altering endogenous calcium signaling and functions in single cells in vitro and in vivo with biochemically controlled subcellular resolution. SpiCee paves the way to investigate local calcium signaling in vivo and directly manipulate this second messenger for therapeutic use. [Display omitted] •Development of SpiCee, a genetically encoded calcium scavenger•SpiCee inhibits calcium-dependent downstream pathways•SpiCee enables cell-specific manipulation of calcium-dependent processes in vivo•Subcellular targeting confers cell compartment specificity to SpiCee Ros et al. develop SpiCee, a genetically encoded calcium chelator that enables the manipulation of this second messenger in single cells with subcellular specificity. SpiCee alters the migration of developing cortical neurons in vivo. Targeting of lipid rafts prevents axonal repulsion, whereas exclusion from this subcellular compartment does not.