University College London, UK
Courier Service for phosphatidylinositol: PITPs deliver on demand
Phosphatidylinositol (PI) is the parent lipid for the synthesis of seven phosphorylated inositol lipids and each of them play specific roles in numerous processes including receptor-mediated phospholipase C signalling, actin cytoskeleton dynamics and membrane traffic. PI synthesis is localised to the endoplasmic reticulum whilst the phosphorylated derivatives of PI are mainly localised in organelles where the lipid kinases also reside. The conversion of PI to phosphorylated derivatives including PI4P and PI(4,5)P2 by lipid kinases in target membranes including the plasma membrane and the Golgi provides for directional transfer. Here I review a family of proteins, phosphatidylinositol transfer proteins (PITPs), that can mobilise PI from the ER to provide the substrate to the resident kinases for phosphorylation. Transfer of PI is coupled to reciprocal transfer of phosphatidylcholine for Class I PITPα and PITPβ or to phosphatidic acid for Class II PITPs. Here I will discuss recent studies that identify specific roles for different PITPs in phospholipase C signalling, neuronal function, membrane traffic and in cancer metastases.