Fig. 2. IP6K inhibition reduces the export of phosphate via an XPR1-dependent mechanism involving the SPX domain.

Effect of treatment with SC-919 for 4 h on the a intracellular InsP₇ levels in 293 cells, b exported extracellular ³²P activity, and c intracellular ³²P activity in the phosphate export assay in 293 cells, d intracellular ³²P activity in the phosphate uptake assay in 293 cells, e, f Levels of InsP₇ in HAP1 wild-type and XPR1 KO cells, g levels of exported extracellular ³²P activity, and h intracellular ³²P activity in phosphate export assay in HAP1 wild-type and XPR1 KO cells, i intracellular ³²P activity in phosphate uptake assay in HAP1 wild-type and XPR1 KO cells, j, k Exported extracellular ³²P activity and intracellular ³²P activity in phosphate export assay in XPR1 KO cells introduced with either eGFP, XPR1, or inositol pyrophosphates-binding site-deleted XPR1 (XPR1ΔSPX) treated with either DMSO or SC-919 (1 μM). Values indicate mean ± S.D. (n = 5 biological replicates for a–f and 6 biological replicates for g–k). ^†P < 0.05 and ^‡P < 0.05 vs. vehicle as determined using Williams’ test and Shirley–Williams test, respectively. **P < 0.01 as determined using Student’s t-test, and ^#P < 0.05 as determined using the Aspin–Welch test. D, DMSO. CPM, counts per minute.