The many functions of ESCRTs

Vietri, Marina; Radulovic, Maja; Stenmark, Harald

doi:10.1038/s41580-019-0177-4

Cited by 707 publications

(728 citation statements)

References 213 publications

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“…Several recent studies have implied a role for the endosomal sorting complexes required for transport (ESCRT) machinery in closure of the phagophore to form an autophagosome. This process shares topology with canonical ESCRT-dependent processes, including multivesicular body formation, virus budding from the plasma membrane, and cytokinesis (Vietri et al, 2020). A possible role for the ESCRTs in phagophore closure was previously suggested, as autophagosomes were found to accumulate in ESCRT-depleted cells (Filimonenko et al, 2007;Lee et al, 2007;Rusten et al, 2007), but owing to technical limitations, it has been difficult to distinguish fully closed autophagosomes from those containing small holes in ESCRT-depleted cells.…”

Section: Autophagosome Closurementioning

confidence: 98%

Autophagosome biogenesis: From membrane growth to closure

Melia

Lystad

Simonsen

2020

Journal of Cell Biology

234

194

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Autophagosome biogenesis involves de novo formation of a membrane that elongates to sequester cytoplasmic cargo and closes to form a double-membrane vesicle (an autophagosome). This process has remained enigmatic since its initial discovery >50 yr ago, but our understanding of the mechanisms involved in autophagosome biogenesis has increased substantially during the last 20 yr. Several key questions do remain open, however, including, What determines the site of autophagosome nucleation? What is the origin and lipid composition of the autophagosome membrane? How is cargo sequestration regulated under nonselective and selective types of autophagy? This review provides key insight into the core molecular mechanisms underlying autophagosome biogenesis, with a specific emphasis on membrane modeling events, and highlights recent conceptual advances in the field.

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Section: Autophagosome Closurementioning

confidence: 98%

Autophagosome biogenesis: From membrane growth to closure

Melia

Lystad

Simonsen

2020

Journal of Cell Biology

234

194

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“…ESCRT proteins are recruited to the site of membrane damage following Ca 2+ influx, at which they form ESCRT complexes that remove the damaged membrane from the cell surface through bleb formation. 46 Broz and colleagues demonstrated that the ESCRT-III complex is recruited to the plasma membrane during pyroptosis and suggested that the ESCRT machinery negatively regulates pyroptosis. 44 A recent study showed that Mg 2+ at high concentrations (5-20 mM) inhibited pyroptosis by limiting the localization of GSDMD p30 to the plasma membrane.…”

Section: Regulation Of Pyroptosismentioning

confidence: 99%

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Tsuchiya

2020

Microbiology and Immunology

179

144

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“…The ESCRT machinery is composed of four protein subcomplexes named ESCRT-0, -I, -II, and -III, and the ATPase Vps4. These assemble sequentially at the limiting membrane of the late endosome (Schuh and Audhya, 2014;Vietri et al, 2019). The ESCRT machinery regulates various cellular processes involved in development (Irion and St Johnston, 2007), neurogenesis (Loncle et al, 2015), virus budding (Carlton et al, 2008), cytokinesis (König et al, 2017;Matias et al, 2015) and autophagy (Lee et al, 2007;Rusten et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Accessory ESCRT-III proteins selectively regulate Rab11-exosome biogenesis inDrosophilasecondary cells

Marie

Fan

Mendes

et al. 2020

Preprint

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Exosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in multivesicular endosomes, which subsequently fuse with the plasma membrane. These ILVs are made in both late endosomes and recycling endosomes, the latter marked by the small GTPase Rab11 and generating exosomes with different cargos and functions. Core proteins within four Endosomal Sorting Complex Required for Transport (ESCRT) assemblies (0-III) play key sequential roles in late endosomal exosome biogenesis and ILV-mediated destruction of ubiquitinylated cargos through the endolysosomal system. They also control additional cellular processes, such as cytokinesis and other vesicle budding.By contrast, the functions of several accessory ESCRTs are not well defined. Here we assess the ESCRT-dependency of Rab11-exosomes, using RNA knockdown in Drosophila secondary cells (SCs) of the male accessory gland, which have unusually enlarged Rab11-positive compartments. Unexpectedly, not only are core proteins in all four ESCRT complexes required for Rab11-exosome formation, but also accessory ESCRT-III proteins, CHMP1, CHMP5 and IST1. Suppressing expression of these accessory proteins does not affect other aspects of cell morphology, unlike most core ESCRT knockdowns, and does not lead to accumulation of ubiquitinylated cargos. We conclude that accessory ESCRT-III components have a specific and potentially ubiquitin-independent role in Rab11-exosome generation, which might provide a target for blocking the pro-tumorigenic activities of these vesicles in cancer.

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The many functions of ESCRTs

Cited by 707 publications

References 213 publications

Autophagosome biogenesis: From membrane growth to closure

Autophagosome biogenesis: From membrane growth to closure

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Accessory ESCRT-III proteins selectively regulate Rab11-exosome biogenesis inDrosophilasecondary cells

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