ESCRT
Encyclopedia
ESCRT 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
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

-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
Invagination
Invagination means to fold inward or to sheath. In biology, this can refer to a number of processes.* Invagination is the morphogenetic processes by which an embryo takes form, and is the initial step of gastrulation, the massive reorganization of the embryo from a simple spherical ball of cells,...

 of the membrane into an internal vesicle also depends on PI(3)P, resulting from the phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 of phosphatidylinositol
Phosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....

 by a lipid kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...

, 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
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

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.
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