How Do Endosomes Degrade Membrane Proteins?
Degrading a membrane protein is not trivial. Soluble proteins that are not anchored into membranes can be degraded by cytoplasmic proteases that belong to the 26S proteosome degradation pathway. But how does a cell degrade a protein that is inserted into a membrane? Most plasma membrane proteins are tagged for degradation by special enzymes called E3 ligases. These ligases attach an ubiquitin molecule to specific lysine residues on the target protein, which identifies the protein as ready for degradation. In many organisms, ubiquitination is enough to trigger internalization of plasma membrane proteins and their subsequent delivery to endosomes (Figure 1). Endosomal protein complexes then recognize ubiquitinated membrane proteins and sort them into vesicles inside the endosomal lumen, giving rise to multivesicular endosomes or MVBs. The endosomal invagination process is quite unique. Unlike most vesiculation processes in which membrane buds protrude into the cytoplasm, the endosomal ve
