A novel mechanism in sphingolipid-mediated phosphoinositide homeostasis at trans-Golgi network
The lipid composition of organelles acts as a landmark to define membrane identity and specify subcellular function. Phosphoinositides are anionic lipids acting in protein sorting and trafficking at the trans-Golgi network (TGN). Sphingolipids are known to control the turnover of the phosphoinositide phosphatidylinositol-4-phosphate (PI4P) through lipid exchange mechanisms at endoplasmic reticulum/TGN contact sites. We discovered a completely new mechanism involving sphingolipids independently from either lipid exchange induced by sphingolipid synthetic flux, or local PI4P synthesis. Instead, we found that sphingolipids mediate the consumption of PI4P through phosphoinositide-specific phospholipase C (PI-PLC) and this process impacts the polar sorting of the auxin efflux carrier PIN2 at the TGN. Together, our data identify a new mode of action of sphingolipids in lipid interplay at the TGN during protein sorting.