Probing metazoan polyphosphate biology using <i>Drosophila</i> reveals novel and conserved polyP functions.

Abstract

Polyphosphate (polyP) exists in all life forms; however, its biological functions in metazoans are understudied. Here, we explored <i>Drosophila,</i> to our knowledge, as the first genetic model to explore polyP biology in metazoans. We established biochemical and in situ methods to detect, quantify, and visualise polyP in <i>Drosophila</i>. We then engineered a FLYX system to deplete polyP in subcellular compartments in a tissue-specific manner. Using these tools, we demonstrated a spatiotemporal and subcellular compartment-specific regulation of polyP levels in various developmental stages and tissue types. We discovered that polyP is crucial for <i>Drosophila</i> hemolymph clotting and proper developmental timing, consistent with an evolutionarily conserved role as exogenous polyP also accelerates mammalian blood clotting. Furthermore, the transcriptomics analysis of polyP-depleted larvae demonstrates the impact of polyP on several cellular processes, including translation. These observations underscore the utility of the toolkit we developed to discover previously unknown polyP functions in metazoans.