Conservation of heat stress acclimation by the inositol polyphosphate multikinase, IPMK responsible for 4/6-InsP7 production in land plants

Inositol pyrophosphates (PP-InsPs) are soluble cellular messengers that integrate environmental cues to induce adaptive responses in eukaryotes. In plants, the biological functions of various PP-InsP species are poorly understood, largely due to the absence of canonical enzymes present in other eukaryotes. The recent identification of a new PP-InsP isomer with yet unknown enantiomeric identity, 4/6-InsP7 in the eudicot Arabidopsis thaliana, further highlights the intricate PP-InsP signalling network employed by plants. The abundance of 4/6-InsP7 in land plants, the enzyme(s) responsible for its synthesis, and the physiological functions of this species are all currently unknown. In this study, we show that 4/6-InsP7 is the major PP-InsP species present across land plants. Our findings demonstrate that the Arabidopsis inositol polyphosphate multikinase (IPMK) homolog, AtIPK2 generates 4/6-InsP7 in vitro. Furthermore, the cellular level of 4/6-InsP7 is controlled by the two Arabidopsis IPMK isoforms, AtIPK2 and AtIPK2{beta}. Notably, the activity of these IPMK proteins is critical for heat stress acclimation in Arabidopsis. During heat stress, the expression of genes encoding various heat shock proteins controlled by the heat shock factors (HSFs) is affected in the AtIPK2-deficient plants. Furthermore, we show that the transcription activity of HSF is regulated by the AtIPK2 proteins. Our parallel investigations using the liverwort Marchantia polymorpha suggest that the InsP6 kinase activity of IPMK and the role of IPMK in regulating the heat stress response are evolutionarily conserved. Collectively, our study indicates that IPMK has played a critical role in transducing environmental cues for biological processes during land plant evolution.