Novel mechanisms in phosphoinositide turnover

Abstract

The hydrolysis of phosphatidylinositol 4,5‐ bisphosphate [PI(4,5)P2] at the plasma membrane by receptor activated phospholipase C (PLC) activity is a conserved mechanism of signal transduction. Given the low abundance of PI(4,5)P2 at the plasma membrane, its hydrolysis needs to be coupled to lipid resynthesis to ensure continued PLC activity during receptor activation. However, the mechanism by which PI(4,5)P2depletion during signalling is coupled to its resynthesis remains unknown. PI(4,5)P2synthesis is catalyzed by lipid kinase activity and the phosphorylation of phosphatidylinositol 4 phosphate (PI4P) by phosphatidylinositol 4 phosphate 5 kinase (PIP5K) is the final step in this process. In Drosophila photoreceptors, sensory transduction of photon absorption is transduced into PLC activity leading to an electrical response to light. During this process, PI(4,5)P2is resynthesized by a PIP5K activity but the mechanism by which the activity of this enzyme is coupled to PLC signalling is not known. In this study, we identify a unique protein isoform of dPIP5K,dPIP5KL that is both necessary and sufficient to mediate PI(4,5)P2synthesis during phototransduction. The activity of dPIP5KLin vitrois enhanced by depletion of PNUT, a non‐redundant subunit of the septin family of GTP binding proteins and in vivo, depletion of dPIP5KL rescues the effect of pnut depletion on the light response and PI(4,5)P2resynthesis during PLC signalling. Thus, our work defines a septin 7 mediated mechanism through which PIP5K activity is coupled to ongoing PLC mediated PI(4,5)P2 depletion.