Arabidopsis inositol phosphate kinases, IPK1 and ITPK1, constitute a metabolic pathway in maintaining phosphate homeostasis

Summary Emerging studies have implicated a close link between inositol phosphate (Ins P ) metabolism and cellular phosphate (P i ) homeostasis in eukaryotes; however, whether a common Ins P species is deployed as an evolutionarily conserved metabolic messenger to mediate P i signaling remains unknown. Here, using genetics and Ins P profiling combined with P i starvation response (PSR) analysis in Arabidopsis thaliana , we showed that the kinase activity of inositol pentakisphosphate 2-kinase (IPK1), an enzyme required for phytate (inositol hexakisphosphates; Ins P 6 ) synthesis, is indispensable for maintaining P i homeostasis under P i -replete conditions, and inositol 1,3,4-trisphosphate 5/6-kinase 1 (ITPK1) plays an equivalent role. Although both ipk1-1 and itpk1 mutants exhibited decreased levels of Ins P 6 and diphosphoinositol pentakisphosphate (PP-Ins P 5 ; Ins P 7 ), disruption of another ITPK family enzyme, ITPK4, which correspondingly caused depletion of Ins P 6 and Ins P 7 , did not display similar P i -related phenotypes, which precludes these Ins P species as effectors. Notably, the level of D/L-Ins(3,4,5,6) P 4 was concurrently elevated in both ipk1-1 and itpk1 mutants, which implies a potential role for Ins P 4 in regulating P i homeostasis. However, the level of D/L-Ins(3,4,5,6) P 4 is not responsive to P i starvation that instead manifests a shoot-specific increase in Ins P 7 level. This study demonstrates a more nuanced picture of intersection of Ins P metabolism and P i homeostasis and PSR than has previously been elaborated, and additionally establishes intermediate steps to phytate biosynthesis in plant vegetative tissues. Significance Statement Regulation of phosphate homeostasis and adaptive responses to phosphate limitation is critical for plant growth and crop yield. Accumulating studies implicate inositol phosphates as regulators of phosphate homeostasis in eukaryotes; however, the relationship between inositol phosphate metabolism and phosphate signaling in plants remain elusive. This study dissected the step where inositol phosphate metabolism intersects with phosphate homeostasis regulation and phosphate starvation responses.