Growing functions of the ESCRT machinery in cell biology and viral replication

Abstract

The vast expansion in recent years of the cellular processes promoted by the endosomal sorting complex required for transport (ESCRT) machinery has reinforced its identity as a modular system that uses multiple adaptors to recruit the core membrane remodelling activity at different intracellular sites and facilitate membrane scission. Functional connections to processes such as the aurora B-dependent abscission checkpoint also highlight the importance of the spatiotemporal regulation of the ESCRT machinery. Here, we summarise the role of ESCRTs in viral budding, and what we have learned about the ESCRT pathway from studying this process. These advances are discussed in the context of areas of cell biology that have been transformed by research in the ESCRT field, including cytokinetic abscission, nuclear envelope resealing and plasma membrane repair.

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

“…The ESCRT pathway mediates membrane fission reactions throughout the cell (Christ et al 2017, Frankel & Audhya 2018, Lippincott-Schwartz et al 2017, Schöneberg et al 2017, Scourfield & Martin-Serrano 2017, Stoten & Carlton 2018) (Figure 1 a ). Cytoplasmic protein complexes like the ESCRT machinery can separate a single continuous lipid bilayer into two discontinuous bilayers via one of two reciprocal orientations: one in which the opposing membranes are drawn together to create a membrane neck that encircles cytoplasm (here termed inside-out membrane fission) and another in which the membrane neck is surrounded by cytoplasm (outside-in membrane fission).…”

“…The ever-growing list of cellular membrane remodeling reactions performed by the ESCRT pathway has been reviewed extensively (Christ et al 2017, Lippincott-Schwartz et al 2017, Schôneberg et al 2017, Scourfield & Martin-Serrano 2017, Stoten & Carlton 2018). Here, we briefly summarize cellular ESCRT functions, highlighting how the machinery functions across a remarkable range of temporal and spatial dimensions and can mediate membrane fission in both possible orientations.…”

ESCRT‐II functions by linking to ESCRT‐I in human immunodeficiency virus‐1 budding

“…Endosomal sorting complexes required for transport (ESCRTs) are a family of cellular proteins comprising ESCRT‐0, ‐I, ‐II, and ‐III complexes and have been reviewed extensively (Olmos & Carlton, ; Schöneberg, Lee, Iwasa, & Hurley, ; Scourfield & Martin‐Serrano, ). Each is composed of two or more proteins: ESCRT‐0 (HRS and STAM complexes), ESCRT‐I (TSG101, VPS28, VPS37, and MVB12/UBAP1), ESCRT‐II (EAP20, EAP30, and EAP45), and ESCRT‐III (CHMP1–7) being the major recognised components.…”

In vitro methods for testing antiviral drugs

“…This is a controlled process that involves both viral protein domains and cellular factors. During this process, viruses apparently use cellular machinery similar to that used during the last step of cell division (the release of the daughter cell) called endosomal sorting complex required for transport (ESCRT) [reviewed in (Campsteijn et al, 2016;Hurley, 2015;Olmos and Carlton, 2016;Scourfield and Martin-Serrano, 2017)]. Direct interactions of numerous viral domains with ESCRT complex subunits have been identified (Bieniasz, 2006).…”