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Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates sugar homeostasis in Drosophila

Karmaker, A.; PADINJAT, R.

2025-12-05 developmental biology
10.64898/2025.12.03.692006 bioRxiv
Show abstract

Metabolic adaptation such as sugar homeostasis is central to the response of living organisms to environmental changes and in insects, sugar homeostasis is an integral part of larval development. Mutants of phosphatidylinositol 5-phosphate 4-kinase (dPIP4K) show altered growth and larval development. We find that dPIP4K mutants (dPIP4K29) show enhanced glucose uptake by the fat body, accompanied by increased circulating trehalose levels in feeding third instar larvae. Following acute starvation on a low sugar diet, dPIP4K29 larvae show reduced survival and accelerated pupariation. This phenotype of dPIP4K29 larvae was associated with high circulating trehalose levels, while under equivalent conditions, wildtype larvae undergo depletion of circulating trehalose. The change in circulating trehalose levels during starvation has been reported to depend on the trehalose transporter Tret1-1PA in brain glial cells. We found that while Tret1-1PA transcripts were upregulated on starvation in wild type flies, there was no such enhancement in dPIP4K29. A glia specific depletion of Tret1-1PA in wild type larvae prevents reduction of circulating trehalose levels upon starvation, phenocopying that seen in dPIP4K29. Together, these findings identify dPIP4K as a key regulator of sugar homeostasis and survival in larvae during starvation.

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