Phosphatidylinositol 4-phosphate gradients shape the lipid landscape of eukaryotic cells
Dr Tamas BALLA
Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Monday, October 14th 2019 - 11 a.m.
- Auditorium, IGBMC
Hosted by Fabien ALPY & Catherine-Laure TOMASETTO
Phosphatidylinositol 4-kinase (PI4K) activity has long been believed to simply provide PI4P for PI(4,5)P2 synthesis in the plasma membrane. However, out of four distinct PI4K enzymes encoded in the mammalian genome only one, PI4KA has been associated with the plasma membrane (PM) and has been linked to PI(4,5)P2 maintenance in the PM. Other PI4Ks, namely PI4KB and the type II PI4Ks (alpha and beta) are localized and function in the Golgi and endosomes, respectively. Recent studies have shown that the high metabolic turnover of PI4P mostly reflects the PI4KA-mediated phosphorylation of phosphatidylinositol (PI) at the PM and Sac1-mediated dephosphorylation of PI4P in the ER. This cycle takes place at contact sites between the PM and ER where the lipids are exchanged by non-vesicular lipid transfer. This PI-PI4P lipid cycle has been linked to phosphatidylserine (PS) transport from the ER to the PM, but many details of the process remains obscure. An important missing information in this cycle is the mechanism by which PI gets from its site of synthesis in the ER to the PM for phosphorylation and how this process is coupled to PI synthesis. These questions are even more relevant in light of the importance of PI4Ks as host factors in replication of several pathogenic viruses making them desirable targets for pharmaceutical companies. We will present our most recent data on the unique features of PI synthesis and on our progress in determining PI distribution in eukaryotic cells.