Mitogenic growth factor receptors such as the epidermal growth factor receptor (EGFR) are tyrosine kinase receptors that are activated by ligand binding. One critical mechanism allowing the control of signalling responses downstream of EGFR is limiting the duration of EGFR activation, a process termed downregulation. Downregulation of EGFR involves its trafficking from the cell surface to the lysosome, where it is degraded.
Once activated, epidermal growth factor receptor is ubiquitinated and delivered to the early endosome. Here it is sorted to intralumenal vesicles, generating a multivesicular body (MVB), en route to being transported to the lysosome. Sorting occurs via a series of ESCRT (Endosomal Sorting Complex Required for Transport) complexes, which cluster ubiquitinated receptors and then incorporate them into intralumenal vesicles. As well as supporting MVB formation, ESCRT complexes regulate other cellular events such as cytokinesis and viral budding.
The seminar will provide an introduction to MVB sorting and focus on three related issues:
1. How might ESCRT-dependent sorting be linked to EGFR signalling?
2. What controls the passage of EGFR through the ESCRT pathway?
3. What is the molecular basis for selective ESCRT function at the endosome?