ESCRTs are everywhere

Abstract

The ESCRT proteins are an ancient system that buds membranes and severs membrane necks from their inner face. Three "classical" functions of the ESCRTs have dominated research into these proteins since their discovery in 2001: the biogenesis of multivesicular bodies in endolysosomal sorting; the budding of HIV-1 and other viruses from the plasma membrane of infected cells; and the membrane abscission step in cytokinesis. The past few years have seen an explosion of novel functions: the biogenesis of microvesicles and exosomes; plasma membrane wound repair; neuron pruning; extraction of defective nuclear pore complexes; nuclear envelope reformation; plus-stranded RNA virus replication compartment formation; and micro- and macroautophagy. Most, and perhaps all, of the functions involve the conserved membrane-neck-directed activities of the ESCRTs, revealing a remarkably widespread role for this machinery through a broad swath of cell biology.

Keywords: exosome; exovesicle; nuclear envelope reformation; plasma membrane wound repair; shedding microvesicle.

Figure 1

Overview of the cellular functions of the ESCRTs

Figure 2

Two branches of the ESCRT pathway The ESCRT-I/ESCRT-II and ALIX branches of the ESCRT pathway are illustrated in the context of a generic vesicle bud neck. The upstream ESCRTs (I/II and ALIX) are shown on the outer face of the bud neck with respect to ESCRT-III; however, the actual nanoscale arrangement of the molecules is unknown.

Figure 3

Viral and vesicular budding by the ESCRTs (A) Budding of HIV-1 from the plasma membrane of an infected human cell uses both ESCRT-I and ALIX. ESCRT-II is shown despite a lack of genetic evidence for its role in HIV-1 budding, because it is capable of bridging ESCRT-I and ESCRT-III in vitro, and a bridging factor of some kind is necessary. (B) ARRDC1 mediates microvesicle budding through the ESCRT-I pathway. (C) Syntenin mediates ALIX recruitment in the biogenesis of syndecan-containing exosomes. (D) T-cell receptor-containing microvesicles are shed into the immunological synapse in an ESCRT-I-dependent process. Vps4 is required in all of these processes but not shown.

Figure 4

Membrane neck scission by ESCRTs in cell division (A) The classical cytokinetic function of both the ESCRT-I/ESCRT-II and ALIX branches of the pathway in membrane abscission, and coordination with microtubule severing by spastin. (B) Resolution of gaps between fragments of reforming nuclear membrane in telophase, again coordinated with microtubule severing. Vps4 is required in both pathways but not shown.