Endosomal sorting: deciding the fate of surface membrane proteins

Plasma membrane proteins destined for degradation are internalised, enter the endosome, and then transit to the lysosome. Many crucial proteins follow this pathway, with epidermal growth factor receptor (EGFR) an exemplar because of its biological and biomedical importance. EGFR transport to the lysosome requires a crucial event; the receptor is ubiquitinated and then enters membrane vesicles that bud into the lumen of the endosome, to form the multivesicular body. The molecular machinery that drives multivesicular body formation 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 escapes itself. The talk will describe our progress towards elucidating this machinery and understanding how it supports EGFR downregulation.