May 3, 2020

A broad response to intracellular long-chain polyphosphate in human cells

BioRxiv : the Preprint Server for Biology
E. Bondy-ChorneyMike Downey


Polyphosphates (PolyP) are highly anionic, linear polymers composed of long chains of inorganic phosphates linked together by phosphoanhydride bonds. PolyP chains are found in all kingdoms of life, and play roles in phosphate homeostasis, cell growth, infection, and blood coagulation. A resurgence in interest in polyP has led to studies showing potential links to diverse aspects of human disease. However, unlike in bacteria and yeast, the mammalian enzymes responsible for the synthesis and degradation of polyP are unknown, which presents a challenge for the study of polyP in higher eukaryotes. Many studies have resorted to adding polyP to cell culture media, but it is not always clear if externally applied polyP enters the cell to impact signaling events or whether their effect is mediated exclusively by extracellular receptors. For the first time, we use RNA-seq and mass spectrometry to define a broad impact of polyP produced inside of mammalian cells via ectopic expression of the E. coli polyP synthetase Ppk1. RNA-seq analysis demonstrates that Ppk1 expression impacts the expression of over >350 genes enriched for processes related to transcription and cell motility. Analysis of proteins via label-free mass spectrometry ident...Continue Reading

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Caenorhabditis elegans
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