Control of XPR1-dependent cellular phosphate efflux by InsP₈ is an exemplar for functionally-exclusive inositol pyrophosphate signaling.

ABSTRACT: Homeostasis of cellular fluxes of inorganic phosphate (Pi) supervises its structural roles in bones and teeth, its pervasive regulation of cellular metabolism, and its functionalization of numerous organic compounds. Cellular Pi efflux is heavily reliant on Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1), regulation of which is largely unknown. We demonstrate specificity of XPR1 regulation by a comparatively uncharacterized member of the inositol pyrophosphate (PP-InsP) signaling family: 1,5-bis-diphosphoinositol 2,3,4,6-tetrakisphosphate (InsP₈). XPR1-mediated Pi efflux was inhibited by reducing cellular InsP₈ synthesis, either genetically (knockout [KO] of diphosphoinositol pentakisphosphate kinases [PPIP5Ks] that synthesize InsP₈) or pharmacologic

SUBMITTER: Li X 

PROVIDER: S-EPMC7035621 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature