Membrane Fission Reactions of the Mammalian ESCRT Pathway

Abstract

The endosomal sorting complexes required for transport (ESCRT) pathway was initially defined in yeast genetic screens that identified the factors necessary to sort membrane proteins into intraluminal endosomal vesicles. Subsequent studies have revealed that the mammalian ESCRT pathway also functions in a series of other key cellular processes, including formation of extracellular microvesicles, enveloped virus budding, and the abscission stage of cytokinesis. The core ESCRT machinery comprises Bro1 family proteins and ESCRT-I, ESCRT-II, ESCRT-III, and VPS4. Site-specific adaptors recruit these soluble factors to assemble on different cellular membranes, where they carry out membrane fission reactions. ESCRT-III proteins form filaments that draw membranes together from the cytoplasmic face, and mechanistic models have been advanced to explain how ESCRT-III filaments and the VPS4 ATPase can work together to catalyze membrane fission.

Cytokinesis in Animal Cells

“…ESCRT proteins are highly conserved and best known for catalyzing membrane fission events both in virus budding and the sorting of receptors into vesicles that bud off into the lumen of the endosome, creating multivesicular bodies (MVBs) (McCullough et al 2013). Four distinct ESCRTs, known as ESCRT-0, -I, -II, and -III, are sequentially recruited to endosomes and the final complex in the pathway, ESCRT-III, provides the core machinery that mediates membrane deformation and fission events during MVB biogenesis (Wollert et al 2009).…”

Negative membrane curvature catalyzes nucleation of endosomal sorting complex required for transport (ESCRT)-III assembly

“…membrane bending | HIV-1 | nanofabrication | superresolution imaging T he endosomal sorting complexes required for transport (ESCRTs) are an ancient and conserved system for membrane scission (1,2). ESCRT membrane remodeling activities are important in the budding of HIV-1 and other viruses from host cell membranes (3); cytokinesis (4); lysosomal transport (5); and more recently discovered functions that include membrane repair, exosome biogenesis, and nuclear envelope reformation (6).…”

“…ESCRT membrane remodeling activities are important in the budding of HIV-1 and other viruses from host cell membranes (3); cytokinesis (4); lysosomal transport (5); and more recently discovered functions that include membrane repair, exosome biogenesis, and nuclear envelope reformation (6). The ESCRTs are unique in that they promote membrane budding and sever membrane necks by working from the inner face of the bud (1,2).…”

“…The ESCRTs consist of the upstream complexes ESCRT-I, ESCRT-II, and ALIX, which recognize cargo, the ESCRT-III complex responsible for membrane scission, and the AAA+ ATPase VPS4, which releases and recycles ESCRT-III (1,2). In this study, we focus on the human ESCRT-III subunit CHMP4B, which is considered a core component of the membrane scission machinery and is essential for HIV-1 budding (7).…”

Interactions of the Human LIP5 Regulatory Protein with Endosomal Sorting Complexes Required for Transport

“…[1][2][3][4][5][6][7][8][9]. ESCRT factors are recruited to their different sites of action by sequential protein-protein and protein-membrane interactions that are initiated by membrane-specific adaptors such as the HRS-STAM complex (multivesicular body vesicle formation), CEP55 (cytokinesis), and retroviral Gag proteins (virus budding).…”