Cell surface receptors such as receptor tyrosine kinases (RTKs) are key players for cell to cell communication and tissue integrity. Once activated by a ligand, the RTKs are ubiquitinated, internalized and transported in the endo-lysosomal system, where they are eventually degraded.
Our lab has previously contributed to the characterization of a molecular machinery, that recognizes these ubiquitinated receptors on endosomes. This molecular machinery is known as endosomal sorting complex required for transport (ESCRT). ESCRT proteins sequester ubiquitinated receptors into microdomains on endosomes and sorts the receptors into intraluminal vesicles. This process substantially contributes to the downregulation of receptor signaling.
Loss or downregulation of essential ESCRT proteins can therefore lead to dysfunctional endosomes with a strong accumulation of receptors on the endosomal surface. These activated receptors can prolong cell signaling and therefore promote cell migration and proliferation. To this date the fate of these aberrant or dysfunctional endosomes is unclear. We address this issue by identifying proteins that are recruited to ESCRT-dysfunctional endosomes and found autophagy to play a major role.