Control of the Cellular Lipid Landscape by Inositol Lipids.

Cellular organization of eukaryotic cells relies upon compartmentalization of their signaling nodes on special membrane platforms forming the various organelles. Unique lipid composition of the different organelle membranes not only defines their identity but also is critical for the proper assembly and functioning of the protein signaling complexes associated with them. Inositol phospholipids (PPIns), a class of regulatory lipids, play a critical role in defining membrane identity and forming membrane microdomains with unique signaling properties. Recent developments in lipid membrane biology revealed that phosphatidylinositol (PI) 4-phosphate (PI4P) gradients and the PI 4-kinases that form them drive non-vesicular transport of several structural lipids against their concentration gradients at membrane contact sites (MCSs). These processes clearly depend on the delivery of PI from its site of synthesis in the ER to the membranes where PI4Ks convert them to PI4P. Therefore, our recent efforts have been focused on the question of how PI synthesis and PI transport systems provide the means of proper PI delivery to their other membrane destinations. In this presentation we will review our recent data on the generation and use of molecular tools to visualize and manipulate PI metabolism and delivery and demonstrate, how they can help us better understand the central role of PPIns in defining the overall lipid landscape of eukaryotic cells.