@article {164007, title = {The multifaceted phosphatidylinositol 5 phosphate 4-kinase proteins: molecular properties and biological functions.}, journal = {Biochim Biophys Acta Mol Cell Biol Lipids}, volume = {1871}, year = {2026}, month = {2026 Jan}, pages = {159698}, abstract = {

Phosphoinositides are regulators of key cell biological processes such as plasma membrane function, vesicular transport, cytoskeletal and nuclear organization. In turn, their levels are tightly controlled by the function of lipid kinases and phosphatases that modify specific hydroxyl groups on the inositol ring. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is one such lipid kinase. Although initially discovered as an enzyme that phosphorylates the 4th hydroxyl on the inositol ring of phosphatidylinositol 5 phosphate (PI5P) with exquisite specificity, it has recently emerged that PIP4K may also work on other substrates. Interestingly, recent studies have also proposed functions for this enzyme that do not require its catalytic activity. Although most elements of phosphoinositide signalling are conserved across all eukaryota, a limited number of phosphoinositide kinases and phosphatases including PIP4K seem to be a unique feature of the genomes of organisms that exist in a multicellular state but not unicellular eukaryotes. Genetic studies in model organisms implicate PIP4K function in key processes such as hormone regulated metabolic control as well as cell division and growth. Consequently, PIP4K function has important biomedical implications in the context of cancer, metabolic syndrome and autoimmune disorders. In this review, we analyze emerging findings on PIP4K function and reflect on the biochemical raison d{\textquoteright}{\^e}tre of how this protein regulates cell physiology in metazoans.

}, keywords = {Animals, Humans, Phosphatidylinositol Phosphates, Phosphotransferases (Alcohol Group Acceptor), Signal Transduction}, issn = {1879-2618}, doi = {10.1016/j.bbalip.2025.159698}, url = {https://pubmed.ncbi.nlm.nih.gov/41130585/}, author = {Krishnan, Harini and Venugopal, Aishwarya and Alex, Preethi and Raghu, Padinjat} } @article {155676, title = {Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors.}, journal = {J Cell Biol}, volume = {224}, year = {2025}, month = {2025 May 05}, abstract = {

Membrane contact sites (MCS) between the plasma membrane (PM) and endoplasmic reticulum (ER) regulate Ca2+ influx. However, the mechanisms by which cells modulate ER-PM MCS density are not understood, and the role of Ca2+, if any, in regulating these is unknown. We report that in Drosophila photoreceptors, MCS density is regulated by the Ca2+ channels, TRP and TRPL. Regulation of MCS density by Ca2+ is mediated by Drosophila extended synaptotagmin (dEsyt), a protein localized to ER-PM MCS and previously shown to regulate MCS density. We find that the Ca2+-binding activity of dEsyt is required for its function in vivo. dEsytCaBM, a Ca2+ non-binding mutant of dEsyt is unable to modulate MCS structure. Further, reconstitution of dEsyt null photoreceptors with dEsytCaBM is unable to rescue ER-PM MCS density and other key phenotypes. Thus, our data supports a role for Ca2+ binding to dEsyt in regulating ER-PM MCS density in photoreceptors thus tuning signal transduction during light-activated Ca2+ influx.

}, keywords = {Animals, Calcium, Calcium Signaling, Cell Membrane, Drosophila melanogaster, Drosophila Proteins, Endoplasmic Reticulum, Photoreceptor Cells, Invertebrate, Synaptotagmins, Transient Receptor Potential Channels}, doi = {10.1083/jcb.202407190}, author = {Nath, Vaisaly R and Krishnan, Harini and Mishra, Shirish and Raghu, Padinjat} } @article {130539, title = {PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase.}, journal = {Life Sci Alliance}, volume = {6}, year = {2023}, month = {2023 Sep}, abstract = {

Phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 5-phosphate (PI5P) are low-abundance phosphoinositides crucial for key cellular events such as endosomal trafficking and autophagy. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) is an enzyme that regulates PI5P in vivo but can act on both PI5P and PI3P in vitro. In this study, we report a role for PIP4K in regulating PI3P levels in Loss-of-function mutants of the only PIP4K gene show reduced cell size in salivary glands. PI3P levels are elevated in and reverting PI3P levels back towards WT, without changes in PI5P levels, can rescue the reduced cell size. mutants also show up-regulation in autophagy and the reduced cell size can be reverted by depleting Atg8a that is required for autophagy. Lastly, increasing PI3P levels in WT can phenocopy the reduction in cell size and associated autophagy up-regulation seen in Thus, our study reports a role for a PIP4K-regulated PI3P pool in the control of autophagy and cell size.

}, keywords = {Animals, Autophagy, Cell Size, Drosophila, Endosomes}, issn = {2575-1077}, doi = {10.26508/lsa.202301920}, author = {Ghosh, Avishek and Venugopal, Aishwarya and Shinde, Dhananjay and Sharma, Sanjeev and Krishnan, Meera and Mathre, Swarna and Krishnan, Harini and Saha, Sankhanil and Raghu, Padinjat} }