RT Journal Article SR Electronic T1 Arabidopsis inositol phosphate kinases, IPK1 and ITPK1, constitute a metabolic pathway in maintaining phosphate homeostasis JF bioRxiv FD Cold Spring Harbor Laboratory SP 270355 DO 10.1101/270355 A1 Hui-Fen Kuo A1 Yu-Ying Hsu A1 Wei-Chi Lin A1 Kai-Yu Chen A1 Teun Munnik A1 Charles A. Brearley A1 Tzyy-Jen Chiou YR 2018 UL http://biorxiv.org/content/early/2018/02/24/270355.abstract AB Emerging studies have implicated a close link between inositol phosphate (InsP) metabolism and cellular phosphate (Pi) homeostasis in eukaryotes; however, whether a common InsP species is deployed as an evolutionarily conserved metabolic messenger to mediate Pi signaling remains unknown. Here, using genetics and InsP profiling combined with Pi 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; InsP6) synthesis, is indispensable for maintaining Pi homeostasis under Pi-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 InsP6 and diphosphoinositol pentakisphosphate (PP-InsP5; InsP7), disruption of another ITPK family enzyme, ITPK4, which correspondingly caused depletion of InsP6 and InsP7, did not display similar Pi-related phenotypes, which precludes these InsP species as effectors. Notably, the level of D/L-Ins(3,4,5,6)P4 was concurrently elevated in both ipk1-1 and itpk1 mutants, which implies a potential role for InsP4 in regulating Pi homeostasis. However, the level of D/L-Ins(3,4,5,6)P4 is not responsive to Pi starvation that instead manifests a shoot-specific increase in InsP7 level. This study demonstrates a more nuanced picture of intersection of InsP metabolism and Pi 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.