Regulation of yeast ESCRT-III membrane scission activity by the Doa4 ubiquitin hydrolase

Johnson, Natalie; West, Matt; Odorizzi, Greg

doi:10.1091/mbc.e16-11-0761

Cited by 16 publications

(44 citation statements)

References 75 publications

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“…It is unclear whether this can simply be explained by a weaker knockdown of these genes in SCs or is the result of a mechanistic difference. Interestingly in yeast, Doa4 (the deubiquitinase for ILV cargo in S. cerevisiae) interacts specifically with ESCRT-III proteins Vps20, Vps24 and Snf7 (yeast Shrb), but does not bind to the ESCRT-II Vps25 (Wolters and Amerik, 2015;Johnson et al, 2017). In flies, Usp8, which produces a strong ubiquitin accumulation phenotype following knockdown ( Fig S5D), appears to be the functional orthologue of Doa4, and might also partially bypass ESCRT-II components in SCs in the cycling of modified cargos during ILV formation.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

Marie

Fan

Mendes

et al. 2020

Preprint

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“…In the process by which ubiquitinated cargo proteins are recruited and clustered, Vps27p may work upstream of the ESCRT-I complex [69,74,82,83]. In support of this, ubiquitin binds directly to Vps27p and deletion of the Vps27p ubiquitin-interacting motif blocks the MVB sorting of a ubiquitinated cargo protein and, significantly, without having any apparent effect on vesicle budding and release into the MVB lumen [13,21,66,84,85]. This MVB sorting defect in Vps27p-deficient cells, coupled with the direct binding of Vps27p to ubiquitin has led to the proposal that Vps27p could be a major sorting receptor for ubiquitinated cargo proteins.…”

Section: The Role Of Vacuolar Protein Sorting 27 In Mvb Sortingmentioning

confidence: 99%

“…Prior to disassembly of the ESCRT-III complexes and fission of the membrane to release an intralumenal vesicle, the ubiquitin must be recycled from ubiquitinated cargo proteins [11,21,41,44,78]. The recycling of ubiquitin from the evaginating membrane into the cytoplasm is carried out by the deubiquitinating enzyme Doa4p.…”

Section: Regulation Of Escrt Machinery In Multivesicular Body Sortingmentioning

confidence: 99%

“…This recycling of ubiquitin prevents the degradation of ubiquitin in the vacuole. Doa4p is not required for vesicle assembly, however, it assists ESCRT-II with the recruitment of the ESCRT-III complex [21,50]. The well-studied components of ESCRT-0,-I,-II and -III and the AAA-ATPase Vps4p together comprise 13 of the 16 proteins encoded by the class E VPS genes, suggesting that more ESCRT complexes remain to be discovered or that some components of known ESCRT complexes are yet to be assigned to a complex [42,79,80].…”

Section: Regulation Of Escrt Machinery In Multivesicular Body Sortingmentioning

confidence: 99%

“…ESCRT machinery also functions in the abscission (last) stage of cytokinesis and during enveloped viral budding. The harmonisation of activities (e.g., membrane remodeling) is performed by ESCRT-III and a few other proteins found on the endosomal limiting membrane, the de-ubiquitinating enzyme Doa4p along and Bro1p [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The regulation of Endosomal Sorting Complex Required for Transport and accessory proteins in multivesicular body sorting and enveloped viral budding - An overview

Ahmed

Akram

Iqbal

et al. 2019

International Journal of Biological Macromolecules

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ESCRT (Endosomal sorting complex required for transport) machinery drives different cellular processes such as endosomal sorting, organelle biogenesis, vesicular trafficking, maintenance of plasma membrane integrity, membrane fission during cytokinesis and enveloped virus budding. The normal cycle of assembly and disassembly of some ESCRT complexes at the membrane requires the AAA-ATPase vacuolar protein sorting 4 (Vps4p). A number of ESCRT proteins are hijacked by clinically significant enveloped viruses including Ebola, and Human Immunodeficiency Virus (HIV) to enable enveloped virus budding and Vps4p provides energy for the disassembly/recycling of these ESCRT proteins. Several years ago, the failure of the terminal budding process of HIV following Vps4 protein inhibition was published; although at that time a detailed understanding of the molecular players was missing. However, later it was acknowledged that the ESCRT machinery has a role in enveloped virus budding from cells due to its role in the multivesicular body (MVB) sorting pathway. The MVB sorting pathway facilitates several cellular activities in uninfected cells, such as the down-regulation of signaling through cell surface receptors as well as the process of viral budding from infected host cells. In this review, we focus on summarising the functional organisation of ESCRT proteins at the membrane and the role of ESCRT machinery and Vps4p during MVB sorting and enveloped viral budding.

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ESCRT-dependent cargo sorting at multivesicular endosomes

Frankel

Audhya

2018

Seminars in Cell & Developmental Biology

133

100

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The endosomal sorting complex required for transport (ESCRT) machinery is composed of five multi-subunit protein complexes, which act cooperatively at specialized endosomes to facilitate the movement of specific cargoes from the limiting membrane into vesicles that bud into the endosome lumen. Over the past decade, numerous proteins, lipids, and RNAs have been shown to be incorporated into intralumenal vesicles (ILVs), but the mechanisms by which these unique cargoes are captured are only now becoming better understood. Here, we discuss the potential roles that the ESCRT machinery plays during cargo sorting at multivesicular endosomes (MVEs).

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Regulation of yeast ESCRT-III membrane scission activity by the Doa4 ubiquitin hydrolase

Abstract: Doa4 is the ubiquitin hydrolase in yeast that deubiquitinates transmembrane proteins sorted by ESCRTs. Results support a model for bidirectional regulation between Doa4 and the ESCRT-III complex.

Cited by 16 publications

References 75 publications

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

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

The regulation of Endosomal Sorting Complex Required for Transport and accessory proteins in multivesicular body sorting and enveloped viral budding - An overview

ESCRT-dependent cargo sorting at multivesicular endosomes

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