ESCRT

ESCRT (endosomal sorting complex required for transport) refers to a series of cytosolic protein complexes called ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III.

Endocytosis and Receptor Down-Regulation
The sequential activities of the ESCRT complexes are required for the recognition and sorting of ubiquitin-modified cargo proteins into the internal vesicles of multivesicular bodies (MVBs). Sorting of membrane cargo proteins into the internal vesicles of a MVB requires one or more ubiquitin tags, which are added to the cytosolic domains of membrane proteins. These ubiquitin tags are recognized by the ESCRT complexes, which bind sequentially and work in concert to pass along the cargo proteins from one complex to the next, sorting the ubiquitylated cargo proteins into subregions of the endosomal membrane for inclusion in an intralumenal MVB vesicle.

Invagination of the membrane into an internal vesicle also depends on PI(3)P, resulting from the phosphorylation of phosphatidylinositol by a lipid kinase, and functioning as another docking site for the ESCRT complexes. The complexes require PI(3)P and ubiquitylated cargo proteins to attach to the endosomal membrane. When another phosphate group is added to PI(3)P, producing PI(3,5)P2, the ESCRT-III complex is able to form a large multimeric aggregation on the membrane, enabling the invagination and pinching-off processes required to form the internal vesicles.