Inorganic Phosphate Export by the Retrovirus Receptor XPR1 in Metazoans

• Inorganic phosphate (Pi) exporter function is present in mammals
• XPR1, a retrovirus receptor, is a cellular Pi exporter in metazoans
• XPR1-mediated Pi export occurs in a wide range of cells, including human stem cells
• XRBD, a soluble polypeptide ligand of XPR1, blocks Pi export

SummaryInorganic phosphate uptake is a universal function accomplished by transporters that are present across the living world. In contrast, no phosphate exporter has ever been identified in metazoans. Here, we show that depletion of XPR1, a multipass membrane molecule initially identified as the cell-surface receptor for xenotropic and polytropic murine leukemia retroviruses (X- and P-MLV), induced a decrease in phosphate export and that reintroduction of various XPR1 proteins, from fruit fly to human, rescued this defect. Inhibition of phosphate export was also obtained with a soluble ligand generated from the envelope-receptor-binding domain of X-MLV in all human cell lines tested, as well as in diverse stem cells and epithelial cells derived from renal proximal tubules, the main site of phosphate homeostasis regulation. These results provide new insights on phosphate export in metazoans and the role of Xpr1 in this function.

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