Cellular Functions and Molecular Mechanisms of the ESCRT Membrane-Scission Machinery

The ESCRT machinery is an evolutionarily conserved machinery for scission of membrane necks from their interior. The ESCRT machinery is a modular system consisting of three subcomplexes named ESCRT-I, -II, and -III. The first two complexes function mainly in protein sorting and in recruitment of ESCRT-III, together with Bro1-domain containing proteins. By contrast, the ESCRT-III complex coordinates the membrane-severing function. The ESCRT machinery is recruited to sites of action by subfunction-specific targeting modules. These factors include ESCRT-0 (MVE formation), CEP55 (cytokinesis), and Gag (virus budding), that are able to associate with ESCRT components and Bro1-domain proteins. ESCRT-III subunits assemble into helical filaments that mediate membrane deformation and scission, in cooperation with the ATPase VPS4. The endosomal sorting complex required for transport (ESCRT) machinery is an assembly of protein subcomplexes (ESCRT I-III) that cooperate with the ATPase VPS4 to mediate scission of membrane necks from the inside. The ESCRT machinery has evolved as a multipurpose toolbox for mediating receptor sorting, membrane remodeling, and membrane scission, with ESCRT-III as the major membrane-remodeling component. Cellular membrane scission processes mediated by ESCRT-III include biogenesis of multivesicular endosomes, budding of enveloped viruses, cytokinetic abscission, neuron pruning, plasma membrane wound repair, nuclear pore quality control, nuclear envelope reformation, and nuclear envelope repair. We describe here the involvement of the ESCRT machinery in these processes and review current models for how ESCRT-III-containing multimeric filaments serve to mediate membrane remodeling and scission. The endosomal sorting complex required for transport (ESCRT) machinery is an assembly of protein subcomplexes (ESCRT I-III) that cooperate with the ATPase VPS4 to mediate scission of membrane necks from the inside. The ESCRT machinery has evolved as a multipurpose toolbox for mediating receptor sorting, membrane remodeling, and membrane scission, with ESCRT-III as the major membrane-remodeling component. Cellular membrane scission processes mediated by ESCRT-III include biogenesis of multivesicular endosomes, budding of enveloped viruses, cytokinetic abscission, neuron pruning, plasma membrane wound repair, nuclear pore quality control, nuclear envelope reformation, and nuclear envelope repair. We describe here the involvement of the ESCRT machinery in these processes and review current models for how ESCRT-III-containing multimeric filaments serve to mediate membrane remodeling and scission. in yeast, allows the secretion of proteins independently of the endoplasmic reticulum; consists of vesicles and tubules surrounded by a cup-shaped membrane. final step of cell division where the intercellular bridge connecting the two daughter cells is cleaved. also known as a microvesicle, an extracellular vesicle derived by budding and shedding from the plasma membrane (PM) without endosomal involvement. 30–100 nm small extracellular vesicle; released from cells after fusion of ILV-containing MVEs with the PM. extracellular vesicle derived by budding and shedding from the PM with or without endosomal involvement. acronym for group-specific antigen; one of three main retroviral proteins in addition to Pol (reverse transcriptase) and Env (envelope protein); Gag is a polyprotein precursor which is cleaved into four separate proteins: capsid protein, matrix protein, nucleocapsid protein, and p6. Together they form the viral core. a small vesicle inside an endosome; generated by invagination and abscission of a part of the limiting membrane of an endosome. domains consisting of highly conserved motifs in Gag proteins of various viruses which play a crucial role in pinching off virus particles from membranes. The term reflects their function late in the virus budding process. also called the multivesicular body (MVB), the MVE is an endosome where intraluminal vesicles have been formed by invaginating and abscising parts of the endosome membrane, giving the endosome a multivesicular appearance. lipid modification of proteins where a myristoyl group, derived from myristic acid, is covalently attached to an N-terminal glycine residue by the enzyme N-myristoyltransferase; myristoylation can anchor a protein to membranes. process by which dendrites and axons from neuronal cells are eliminated, resulting in fewer synaptic connections: a physiologic process thought to increase the efficiency of neuronal transmission; is also required for learning. also known as the nuclear membrane, nucleolemma, or karyotheca; the NE is double lipid bilayer membrane which surrounds the nucleus in eukaryotic cells. a protein complex forming a channel in the NE that mediates transport between the nucleoplasm and cytoplasm. an ATP-dependent enzyme of the AAA + protein family which catalyzes the dissociation of ESCRT proteins from membranes and contributes to the membrane remodeling function of ESCRTs. enveloped viruses mature by budding at cellular membranes; thereby they acquire a host-derived membrane enriched in viral proteins to form their external envelope.