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

2017 ◽  
Vol 45 (3) ◽  
pp. 613-634 ◽  
Author(s):  
Edward J. Scourfield ◽  
Juan Martin-Serrano
Keyword(s):  
Cell Biology ◽  
Modular System ◽  
Membrane Repair ◽  
Endosomal Sorting ◽  
Cellular Processes ◽  
Functional Connections ◽  
Escrt Machinery ◽  
Viral Budding ◽  
Spatiotemporal Regulation ◽  
Plasma Membrane Repair

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.

scholarly journals The VPS-20 subunit of the endosomal sorting complex ESCRT-III exhibits an open conformation in the absence of upstream activation

2015 ◽  
Vol 466 (3) ◽  
pp. 625-637 ◽  
Author(s):  
Amber L. Schuh ◽  
Michael Hanna ◽  
Kyle Quinney ◽  
Lei Wang ◽  
Ali Sarkeshik ◽  
...  
Keyword(s):  
Membrane Repair ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Cell Extracts ◽  
Open Conformation ◽  
Membrane Reorganization ◽  
Plasma Membrane Repair ◽  
Retroviral Budding ◽  
Vacuolar Protein

Members of the endosomal sorting complex required for transport (ESCRT) machinery function in membrane remodelling processes during multivesicular endosome (MVE) biogenesis, cytokinesis, retroviral budding and plasma membrane repair. During luminal vesicle formation at endosomes, the ESCRT-II complex and the ESCRT-III subunit vacuolar protein sorting (VPS)-20 play a specific role in regulating assembly of ESCRT-III filaments, which promote vesicle scission. Previous work suggests that Vps20 isoforms, like other ESCRT-III subunits, exhibits an auto-inhibited closed conformation in solution and its activation depends on an association with ESCRT-II specifically at membranes [1]. However, we show in the present study that Caenorhabditis elegans ESCRT-II and VPS-20 interact directly in solution, both in cytosolic cell extracts and in using recombinant proteins in vitro. Moreover, we demonstrate that purified VPS-20 exhibits an open extended conformation, irrespective of ESCRT-II binding, in contrast with the closed auto-inhibited architecture of another ESCRT-III subunit, VPS-24. Our data argue that individual ESCRT-III subunits adopt distinct conformations, which are tailored for their specific functions during ESCRT-mediated membrane reorganization events.

Cell Polarity and Migration: Emerging Role for the Endosomal Sorting Machinery

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 171-180 ◽  
Author(s):  
Viola Hélène Lobert ◽  
Harald Stenmark
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
Cell Polarity ◽  
Tumor Suppressors ◽  
Potential Role ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Viral Budding ◽  
And Migration

The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in the regulation of endosomal sorting, cell division, viral budding, autophagy, and cell signaling. Here, we review recent evidence that implicates ESCRTs in cell polarity and cell migration, and discuss the potential role of ESCRTs as tumor suppressors.

scholarly journals Interdisciplinary Synergy to Reveal Mechanisms of Annexin-Mediated Plasma Membrane Shaping and Repair

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1029 ◽  
Author(s):  
Poul Martin Bendix ◽  
Adam Cohen Simonsen ◽  
Christoffer D. Florentsen ◽  
Swantje Christin Häger ◽  
Anna Mularski ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Biology ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Interdisciplinary Approach ◽  
Membrane Repair ◽  
Cell Membrane Integrity ◽  
Curvature Sensing ◽  
Plasma Membrane Repair ◽  
Curved Membranes

The plasma membrane surrounds every single cell and essentially shapes cell life by separating the interior from the external environment. Thus, maintenance of cell membrane integrity is essential to prevent death caused by disruption of the plasma membrane. To counteract plasma membrane injuries, eukaryotic cells have developed efficient repair tools that depend on Ca2+- and phospholipid-binding annexin proteins. Upon membrane damage, annexin family members are activated by a Ca2+ influx, enabling them to quickly bind at the damaged membrane and facilitate wound healing. Our recent studies, based on interdisciplinary research synergy across molecular cell biology, experimental membrane physics, and computational simulations show that annexins have additional biophysical functions in the repair response besides enabling membrane fusion. Annexins possess different membrane-shaping properties, allowing for a tailored response that involves rapid bending, constriction, and fusion of membrane edges for resealing. Moreover, some annexins have high affinity for highly curved membranes that appear at free edges near rupture sites, a property that might accelerate their recruitment for rapid repair. Here, we discuss the mechanisms of annexin-mediated membrane shaping and curvature sensing in the light of our interdisciplinary approach to study plasma membrane repair.

scholarly journals Why Cells and Viruses Cannot Survive without an ESCRT

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 483
Author(s):  
Arianna Calistri ◽  
Alberto Reale ◽  
Giorgio Palù ◽  
Cristina Parolin
Keyword(s):  
Endosomal Sorting ◽  
Cellular Processes ◽  
Escrt Machinery ◽  
Cellular Environment ◽  
Intracellular Parasites ◽  
Cell Life ◽  
Infected Cells ◽  
Intracellular Organelles ◽  
Simplex Virus ◽  
Hsv 1

Intracellular organelles enwrapped in membranes along with a complex network of vesicles trafficking in, out and inside the cellular environment are one of the main features of eukaryotic cells. Given their central role in cell life, compartmentalization and mechanisms allowing their maintenance despite continuous crosstalk among different organelles have been deeply investigated over the past years. Here, we review the multiple functions exerted by the endosomal sorting complex required for transport (ESCRT) machinery in driving membrane remodeling and fission, as well as in repairing physiological and pathological membrane damages. In this way, ESCRT machinery enables different fundamental cellular processes, such as cell cytokinesis, biogenesis of organelles and vesicles, maintenance of nuclear–cytoplasmic compartmentalization, endolysosomal activity. Furthermore, we discuss some examples of how viruses, as obligate intracellular parasites, have evolved to hijack the ESCRT machinery or part of it to execute/optimize their replication cycle/infection. A special emphasis is given to the herpes simplex virus type 1 (HSV-1) interaction with the ESCRT proteins, considering the peculiarities of this interplay and the need for HSV-1 to cross both the nuclear-cytoplasmic and the cytoplasmic-extracellular environment compartmentalization to egress from infected cells.

scholarly journals MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis

2012 ◽  
Vol 23 (22) ◽  
pp. 4347-4361 ◽  
Author(s):  
Seongju Lee ◽  
Jaerak Chang ◽  
Benoît Renvoisé ◽  
Anita Tipirneni ◽  
Sarah Yang ◽  
...  
Keyword(s):  
Critical Role ◽  
Multivesicular Body ◽  
Strong Interactions ◽  
Body Protein ◽  
Endosomal Sorting ◽  
Cellular Processes ◽  
Viral Budding ◽  
Membrane Fission ◽  
Downstream Effects ◽  
Trafficking Molecules

Diverse cellular processes, including multivesicular body formation, cytokinesis, and viral budding, require the sequential functions of endosomal sorting complexes required for transport (ESCRTs) 0 to III. Of these multiprotein complexes, ESCRT-III in particular plays a key role in mediating membrane fission events by forming large, ring-like helical arrays. A number of proteins playing key effector roles, most notably the ATPase associated with diverse cellular activities protein VPS4, harbor present in microtubule-interacting and trafficking molecules (MIT) domains comprising asymmetric three-helical bundles, which interact with helical MIT-interacting motifs in ESCRT-III subunits. Here we assess comprehensively the ESCRT-III interactions of the MIT-domain family member MITD1 and identify strong interactions with charged multivesicular body protein 1B (CHMP1B), CHMP2A, and increased sodium tolerance-1 (IST1). We show that these ESCRT-III subunits are important for the recruitment of MITD1 to the midbody and that MITD1 participates in the abscission phase of cytokinesis. MITD1 also dimerizes through its C-terminal domain. Both types of interactions appear important for the role of MITD1 in negatively regulating the interaction of IST1 with VPS4. Because IST1 binding in turn regulates VPS4, MITD1 may function through downstream effects on the activity of VPS4, which plays a critical role in the processing and remodeling of ESCRT filaments in abscission.

scholarly journals ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation

Science ◽  
2018 ◽  
Vol 362 (6417) ◽  
pp. 956-960 ◽  
Author(s):  
Sebastian Rühl ◽  
Kateryna Shkarina ◽  
Benjamin Demarco ◽  
Rosalie Heilig ◽  
José Carlos Santos ◽  
...  
Keyword(s):  
Calcium Influx ◽  
Inflammasome Activation ◽  
Membrane Repair ◽  
Cellular Survival ◽  
Endosomal Sorting ◽  
Membrane Pores ◽  
Escrt Machinery ◽  
Inflammatory Caspases ◽  
Survival Mechanisms ◽  
Insight Into

Pyroptosis is a lytic form of cell death that is induced by inflammatory caspases upon activation of the canonical or noncanonical inflammasome pathways. These caspases cleave gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment, which executes pyroptosis by forming membrane pores. We found that calcium influx through GSDMD pores serves as a signal for cells to initiate membrane repair by recruiting the endosomal sorting complexes required for transport (ESCRT) machinery to damaged membrane areas, such as the plasma membrane. Inhibition of the ESCRT-III machinery strongly enhances pyroptosis and interleukin-1β release in both human and murine cells after canonical or noncanonical inflammasome activation. These results not only attribute an anti-inflammatory role to membrane repair by the ESCRT-III system but also provide insight into general cellular survival mechanisms during pyroptosis.

scholarly journals Exosome Biogenesis in the Protozoa Parasite Giardia lamblia: A Model of Reduced Interorganellar Crosstalk

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1600 ◽  
Author(s):  
Sofía Moyano ◽  
Juliana Musso ◽  
Constanza Feliziani ◽  
Nahuel Zamponi ◽  
Lorena Soledad Frontera ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Giardia Lamblia ◽  
Cell Biology ◽  
De Novo ◽  
Cell Communication ◽  
Protozoan Parasite ◽  
Endosomal Sorting ◽  
Aaa Atpase ◽  
Escrt Machinery ◽  
Exosome Biogenesis

Extracellular vesicles (EVs) facilitate intercellular communication and are considered a promising therapeutic tool for the treatment of infectious diseases. These vesicles involve microvesicles (MVs) and exosomes and selectively transfer proteins, lipids, mRNAs, and microRNAs from one cell to another. While MVs are formed by extrusion of the plasma membrane, exosomes are a population of vesicles of endosomal origin that are stored inside the multivesicular bodies (MVBs) as intraluminal vesicles (ILVs) and are released when the MVBs fuse with the plasma membrane. Biogenesis of exosomes may be driven by the endosomal sorting complex required for transport (ESCRT) machinery or may be ESCRT independent, and it is still debated whether these are entirely separate pathways. In this manuscript, we report that the protozoan parasite, Giardia lamblia, although lacking a classical endo-lysosomal pathway, is able to produce and release exosome-like vesicles (ElV). By using a combination of biochemical and cell biology analyses, we found that the ElVs have the same size, shape, and protein and lipid composition as exosomes described for other eukaryotic cells. Moreover, we established that some endosome/lysosome peripheral vacuoles (PVs) contain ILV during the stationary phase. Our results indicate that ILV formation and ElV release depend on the ESCRT-associated AAA+-ATPase Vps4a, Rab11, and ceramide in this parasite. Interestingly, EIV biogenesis and release seems to occur in Giardia despite the fact that this parasite has lost most of the ESCRT machinery components during evolution and is unable to produce ceramide de novo. The differences in protozoa parasite EV composition, origin, and release may reveal functional and structural properties of EVs and, thus, may provide information on cell-to-cell communication and on survival mechanisms.

ESCRT Machinery Is Required for Plasma Membrane Repair

Science ◽  
2014 ◽  
Vol 343 (6174) ◽  
pp. 1247136-1247136 ◽  
Author(s):  
A. J. Jimenez ◽  
P. Maiuri ◽  
J. Lafaurie-Janvore ◽  
S. Divoux ◽  
M. Piel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Repair ◽  
Escrt Machinery ◽  
Plasma Membrane Repair
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