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Regulator of Vps4 activity in the MVB pathway ESCRT-I, -II, and -III are endosomal sorting complexes required for transporting proteins and carry out cargo sorting and vesicle formation in the multivesicular bodies, MVBs, pathway. These complexes are transiently recruited from the cytoplasm to the endosomal membrane where they bind transmembrane proteins previously marked for degradation by mono-ubiquitination. Assembly of ESCRT-III, a complex composed of at least four subunits (Vps2, Vps24, Vps20, Snf7), is intimately linked with MVB vesicle formation, its disassembly being an essential step in the MVB vesicle formation, a reaction that is carried out by Vps4, an AAA-type ATPase. The family Ist1 is a regulator of Vps4 activity; by interacting with Did2 and Vps4, Ist1 appears to regulate the recruitment and oligomerization of Vps4. Together Ist1, Did2, and Vta1 form a network of interconnected regulatory proteins that modulate Vps4 activity, thereby regulating the flow of cargo through the MVB pathway. |
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