The endosomal sorting complexes required for transport (ESCRT) machinery is made up of cytosolic protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm.[1][2] These ESCRT components have been isolated and studied in a number of organisms including yeast and humans.[3] A eukaryotic signature protein, the machinery is found in all eukaryotes and some archaea.[4]
The ESCRT machinery plays a vital role in a number of cellular processes including multivesicular body (MVB) biogenesis, cellular abscission, and viral budding. Multivesicular body (MVB) biogenesis is a process in which ubiquitin-tagged proteins enter organelles called endosomes via the formation of vesicles. This process is essential for cells to destroy misfolded and damaged proteins.[5] Without ESCRT machinery, these proteins can build up and lead to neurodegenerative disease. For example, abnormalities in ESCRT-III components can lead to neurological disorders such as hereditary spastic paraplegia (HSP).[6] Cellular abscission, the process by which the membrane connecting two daughter cells is cleaved, is also mediated by ESCRT machinery. Without the ESCRT complexes, daughter cells could not separate and abnormal cells containing twice the amount of DNA would be generated. These cells would inevitably be destroyed through a process known as apoptosis. Lastly, viral budding, or the process by which specific types of viruses exit cells, may not occur in the absence of ESCRT machinery. This would inevitably prevent viruses from spreading from cell to cell.
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