New insights into endocytic trafficking

Project Summary

Effective drug delivery depends on delivering drugs to the sites in the cell where they are therapeutically active. The goal of this project is to gain a fundamental understanding of how nanoparticles are trafficked in cells.

In particular, we focus on understanding how nanoparticles and their cargo are internalised, trafficked in the endosome and trafficked from the endosome into the cytoplasm (i.e. endosomal escape).

We have focused on fundamental aspects of trafficking to the endosome and the role of endosomal structure in endosomal function. We have previously identified the crucial regulator of endosomal trafficking, Rab5, and its effector EEA1.

We have now shown using state of the art electron microscopy, that EEA1 forms long filaments that extend out from the surface of the endosome.

These filaments bind Rab5 on incoming vesicles causing a conformational change in the EEA1 that allows vesicle fusion.