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Phosphatidylinositol 5 phosphate 4 kinase regulates phosphatidylinositol 3,4 bisphosphate levels in vivo.

Venugopal, A.; Varma, S.; PADINJAT, R.

2025-11-26 cell biology
10.1101/2025.11.24.690171 bioRxiv
Show abstract

In Drosophila, loss of phosphatidylinositol 5 phosphate 4 kinase (PIP4K) results in a reduction in larval salivary gland cell size. Previous studies have shown that this reduction in cell size is not correlated with the levels of phosphatidylinositol 5 phosphate (PI5P), the canonical substrate of PIP4K but to the levels of phosphatidylinositol 3 phosphate (PI3P) a substrate that is used less effectively by the PIP4K enzyme in vitro. The phosphorylation of PI3P by PIP4K generates phosphatidylinositol 3,4 bisphosphate [PI(3,4)P2]. Using a biosensor for PI(3,4)P2, surprisingly, we find that depletion of PIP4K leads to an elevation of intracellular PI(3,4)P2 punctae in salivary gland cells. This elevation in PI(3,4)P2 punctae was not dependent on the catalytic activity of dPIP4K. Rather, we found that the elevation of PI(3,4)P2 was dependent on the catalytic activity of Class II phosphatidylinositol 3 kinase (Class II PI3K). Thus, the PIP4K protein regulates an intracellular pool of PI(3,4)P2 via Class II PI3K activity in Drosophila cells.

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