The ubiquitin code and its decoding machinery in the endocytic pathway.

The level of individual plasma membrane proteins needs to be regulated strictly depending on the situation under which the cell is placed. To reduce the level of a specific plasma membrane protein in a short period, cells internalize the protein from the cell surface by endocytosis and degrade it in the lysosome. Internalized cargo proteins are transported to the limiting membrane of the early endosome, from which they are incorporated into the lumenal vesicles of the endosome. Such endosomes, called the late endosome or multivesicular body, fuse with the lysosome, thereby delivering cargo proteins to the lysosomal lumen and exposing them to acid hydrolases. During this lysosomal trafficking process, ubiquitination serves as a signal that drives internalization and endosome-to-lysosome transport of the cargo proteins. In this review, we discuss the types of ubiquitination that drive these trafficking processes, and how the ubiquitin (Ub) modifications are recognized by specific Ub-binding proteins.