ESCRT

The endosomal sorting complexes required for transport (ESCRT) proteins are part of a pathway inside cells that helps sort and move other proteins. One of their main jobs is to form structures called multivesicular bodies (MVBs) which help sending of certain proteins, especially ones tagged for removal, to compartments in the cell called lysosomes where they get broken down.

The ESCRT system is made up of five separate cytosolic, peripheral membrane protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III and Vps4. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes budding away from the cytoplasm. These ESCRT components have been isolated and studied in a number of organisms including yeast and humans.

The ESCRT machinery plays a vital role in a number of cellular processes including multivesicular body (MVB) biogenesis and cytokinetic abscission. Multivesicular body (MVB) biogenesis is a process in which ubiquitin-tagged proteins enter organelles called endosomes via the formation of vesicles. Cells break down damaged membrane proteins within two main complexes: the proteasome and the lysosome. A small tag called ubiquitin gets attached to them. The tag leads proteins to either the proteasome or the lysosome for destruction. For the lysosomal route the tagged proteins are sent into small compartments inside the cell called endosomes, specifically a kind called multivesicular bodies (MVBs), MVBs are made when part of the endosome membrane folds inward and forms intralumenal vesicles. These intraluminal vesicles carry the proteins meant to be destroyed, and when an MVB joins with a lysosome, the vesicles and the proteins inside get broken down.

When autophagy does not work well like in cells with ESCRT mutations the cell cannot get rid of clumps of damaged proteins very well. These protein clumps are commonly seen in neurodegenerative disease like Alzheimer's or Parkinson's.

Cytokinetic abscission is the process where the intercellular bridge (ICB) between two daughter cells is cut, completing cell division. In many animal cells, the ESCRT-III machinery is responsible for this process. The ICB is initially under high tension, which can prevent proper abscission in epithelial cells by interfering with the assembly of ESCRT-III.