PIP4K2A

Polar auxin transport in the Arabidopsis (Arabidopsis thaliana) root tip maintains high auxin levels around the stem cell niche that gradually decrease in dividing cells but increase again once they transition towards differentiation. Protophloem differentiates earlier than other proximal tissues and employs a unique auxin 'canalization' machinery that is thought to balance auxin efflux with retention. It consists of a proposed activator of PIN-FORMED (PIN) auxin efflux carriers, the AGC kinase PROTEIN KINASE ASSOCIATED WITH BRX (PAX); its inhibitor, BREVIS RADIX (BRX); and PHOSPHATIDYLINOSITOL-4-PHOSPHATE-5-KINASE (PIP5 K) enzymes, which promote polar PAX and BRX localization. Because of dynamic PAX-BRX-PIP5 K interplay, the net cellular output of this machinery remains unclear. Here we deciphered the dosage-sensitive regulatory interactions between PAX, BRX and PIP5 K by their ectopic expression in developing xylem vessels. The data suggest that the dominant collective output of the PAX-BRX-PIP5 K module is a localized reduction in PIN abundance. This requires PAX-stimulated clathrin-mediated PIN endocytosis by site-specific phosphorylation, which distinguishes PAX from other AGC kinases. Ectopic assembly of the PAX-BRX-PIP5 K module is sufficient to cause cellular auxin retention and affects root growth vigor by accelerating the trajectory of xylem vessel development. Our data thus provide direct evidence that local manipulation of auxin efflux alters the timing of cellular differentiation in the root.

To explore the function of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) in tomatoes, members of the tomato PIP5K family were identified and characterized using bioinformatic methods, and their expression patterns were also analyzed under salt stress and in different tissues. Twenty-one PIP5K members-namely, SlPIP5K1-SlPIP5K21-were identified from ten chromosomes, and these were divided into three groups according to a phylogenetic analysis. Further bioinformatic analysis showed four pairs of collinear relationships and fragment replication events among the SlPIP5K family members. To understand the possible roles of the SlPIP5Ks, a cis-acting element analysis was conducted, which indicated that tomato PIP5Ks could be associated with plant growth, hormones, and stress responses. We further validated the results of the in silico analysis by integrating RNA-seq and qRT-PCR techniques for salt- and hormone-treated tomato plants. Our results showed that SlPIP5K genes exhibited tissue- and treatment-specific patterns, and some of the SlPIP5Ks exhibited significantly altered expressions after our treatments, suggesting that they might be involved in these stresses. We selected one of the SlPIP5Ks that responded to our treatments, SlPIP5K2, to further understand its subcellular localization. Our results showed that SlPIP5K2 was located on the membrane. This study lays a foundation for the analysis of the biological functions of the tomato SlPIP5K genes and can also provide a theoretical basis for the selection and breeding of new tomato varieties and germplasm innovation, especially under salt stress.

Solute carrier family 27 member 5, a key enzyme in fatty acid transport and bile acid metabolism in the liver, is frequently expressed in low quantities in patients with hepatocellular carcinoma, resulting in poor prognosis. However, it is unclear whether SLC27A5 plays non-canonical functions and regulates HCC progression. Here, an unexpected non-canonical role of SLC27A5 is reported: regulating the alternative splicing of mRNA to inhibit the metastasis of HCC independently of its metabolic enzyme activity. Mechanistically, SLC27A5 interacts with IGF2BP3 to prevent its translocation into the nucleus, thereby inhibiting its binding to target mRNA and modulating PIP4K2A pre-mRNA splicing. Loss of SLC27A5 results in elevated levels of the PIP4K2A-S isoform, thus positively regulating phosphoinositide 3-kinase signaling via enhanced p85 stability in HCC. SLC27A5 restoration by AAV-Slc27a5 or IGF2BP3 RNA decoy oligonucleotides exerts an inhibitory effect on HCC metastasis with reduced expression of the PIP4K2A-S isoform. Therefore, PIP4K2A-S may be a novel target for treating HCC with SLC27A5 deficiency.