FAPPs involvement in the formation of post Golgi complex carriers

D'Angelo, Giovanni (2008). FAPPs involvement in the formation of post Golgi complex carriers. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00010007

Abstract

The molecular machinery responsible for the generation of transport carriers that move cargo from the Golgi complex to the plasma membrane relies on a tight physical and functional interplay between proteins and lipids. Among the lipid-binding proteins composing this machinery, we previously identified the four-phosphate adaptor proteins FAPP1 and FAPP2 (FAPPs), the pleckstrin homology domain of which binds phosphatidylinositol 4-phosphate and the small GTPase ARF1. FAPP2 also possesses a glycolipid-transfer protein homology domain the function of which remained to be defined. Here, I show that FAPP2 is indeed a cytosolic glucosylceramide-transfer protein and that it has a pivotal role in the synthesis of complex glycosphingolipids, essential components of the plasma membrane and fundamental elements in cell signalling, adhesion and proliferation. Importantly, the requirement for FAPP2 makes the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. Thus, by coupling the synthesis of glycosphingolipids at the Golgi complex with their export towards the plasma membrane, FAPP2 turns out to be a key player in determining the lipid identity of post-Golgi carriers and of the plasma membrane itself, which is highly enriched in glycosphingolipids in comparison to other cell membranes.