ESCRT

ESCRT stands for Endosomal Sorting Complexes Required for Transport. It refers to a set of protein complexes that mediate membrane remodeling events, most notably the sorting of ubiquitinated transmembrane proteins into intraluminal vesicles within late endosomes, a process that forms multivesicular bodies. This pathway helps regulate receptor signaling, receptor downregulation, and cargo turnover, and it also participates in various other cellular remodeling events.

The core ESCRT machinery comprises four main complexes, ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III, along with the Vps4 ATPase. ESCRT-0 binds ubiquitinated cargo and concentrates it on the endosomal membrane; ESCRT-I and ESCRT-II promote membrane invagination and cargo sorting; ESCRT-III assembles into filaments that drive membrane scission to form intraluminal vesicles; Vps4 then disassembles and recycles ESCRT-III subunits. The process is generally sequential, with each complex coordinating the budding and scission steps required to bud vesicles away from the limiting membrane of endosomes.

Beyond endosomal sorting, ESCRT is involved in other membrane remodeling events, including cytokinesis, repair of damaged plasma membranes, and the budding of several enveloped viruses such as HIV-1, which hijack the ESCRT machinery to pinch off new viral particles from the host cell surface.

Historically, ESCRT components were discovered through yeast genetics and are conserved across eukaryotes, reflecting an essential and broad role in cellular homeostasis. Dysfunction or misregulation of ESCRT pathways can impact cell division, trafficking, and signaling, and has been linked to various diseases and conditions, making ESCRT a focal point in cell biology and virology research.