Endosomal sorting: deciding the fate of surface membrane proteins

Plasma membrane proteins destined for degradation are internalised. They enter the endosome and move to the lysosome. Many crucial proteins follow this pathway, including epidermal growth factor receptor (EGFR). Transport to the lysosome requires the receptor to be ubiquitinated and enter membrane vesicles to form the multivesicular body. The molecular machinery that drives the formation of the multivesicular body must overcome a complex topological problem: it recognises ubiquitinated EGFR on the cytoplasmic face of the endosome, generates vesicles that capture EGFR inside the endosome, but then escapes. How this works remains a mystery.

We will reassemble the machinery from its component parts on artificial endosomes and determine how it envelops EGFR. We will also examine how the machinery is activated by EGFR and ensures its efficient capture.