scholarly journals “Repair Me if You Can”: Membrane Damage, Response, and Control from the Viral Perspective

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2042 ◽  
Author(s):  
Coralie F. Daussy ◽  
Harald Wodrich
Keyword(s):  
Current Knowledge ◽  
Membrane Damage ◽  
Cellular Responses ◽  
Cellular Membrane ◽  
Enveloped Viruses ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Damage Response ◽  
And Control ◽  
Specific Membrane

Cells are constantly challenged by pathogens (bacteria, virus, and fungi), and protein aggregates or chemicals, which can provoke membrane damage at the plasma membrane or within the endo-lysosomal compartments. Detection of endo-lysosomal rupture depends on a family of sugar-binding lectins, known as galectins, which sense the abnormal exposure of glycans to the cytoplasm upon membrane damage. Galectins in conjunction with other factors orchestrate specific membrane damage responses such as the recruitment of the endosomal sorting complex required for transport (ESCRT) machinery to either repair damaged membranes or the activation of autophagy to remove membrane remnants. If not controlled, membrane damage causes the release of harmful components including protons, reactive oxygen species, or cathepsins that will elicit inflammation. In this review, we provide an overview of current knowledge on membrane damage and cellular responses. In particular, we focus on the endo-lysosomal damage triggered by non-enveloped viruses (such as adenovirus) and discuss viral strategies to control the cellular membrane damage response. Finally, we debate the link between autophagy and inflammation in this context and discuss the possibility that virus induced autophagy upon entry limits inflammation.

scholarly journals The Dictyostelium discoideum E3 ubiquitin ligase TrafE coordinates endolysosomal damage response and cell-autonomous immunity to Mycobacterium marinum.

2021 ◽  
Author(s):  
Lyudmil Raykov ◽  
Manon Mottet ◽  
Jahn Nitschke ◽  
Thierry Soldati
Keyword(s):  
Cell Death ◽  
Dictyostelium Discoideum ◽  
Cellular Response ◽  
Membrane Damage ◽  
Mycobacterium Marinum ◽  
Chemical Components ◽  
Key Factors ◽  
Endosomal Sorting ◽  
Damage Response ◽  
Intracellular Compartments

Cells are perpetually challenged by pathogens, protein aggregates or chemicals, that induce plasma membrane or endolysosomal compartments damage. Endolysosomal perforations are recognised as severe stress, however the mechanisms of the cellular response that ensure quality control, repair and endolysosomal homeostasis are just beginning to be unravelled. The endosomal sorting complex required for transport (ESCRT) and the autophagy machinery are recruited to damaged membranes to either repair or to remove membrane remnants. Crucial element of the endolysosomal damage response (ELDR) are factors that sense damage, paralleled by extensive tagging of the damaged organelles with signals, such as ubiquitin, required for the recruitment of ELDR components. Unattended membrane damage leads to leakage of harmful components including protons and reactive oxygen species that cause cell death. To explore ELDR key factors responsible for detection and marking of damaged compartments we use the professional phagocyte Dictyostelium discoideum. We found an evolutionary conserved E3-ligase TrafE that is robustly recruited to intracellular compartments disrupted after infection with Mycobacterium marinum or after sterile damage caused by chemical components. Importantly, we show that the absence of TrafE severely compromises the xenophagy restriction of bacteria as well as autophagy-mediated and ESCRT-mediated ELDR, resulting in early cell death.

scholarly journals A Duplicated ESCRT-III Factor Blocks Enveloped Virus Budding Without Inhibiting Cellular ESCRT Functions

2020 ◽  
Author(s):  
Lara Rheinemann ◽  
Diane Miller Downhour ◽  
Kate Bredbenner ◽  
Gaelle Mercenne ◽  
Kristen A. Davenport ◽  
...  
Keyword(s):  
Cellular Membrane ◽  
New World Monkeys ◽  
Virus Budding ◽  
Enveloped Viruses ◽  
Endosomal Sorting ◽  
Adaptive Mutations ◽  
Enveloped Virus ◽  
Viral Budding ◽  
Membrane Fission ◽  
Infected Cells

SummaryMany enveloped viruses require the endosomal sorting complexes required for transport (ESCRT) pathway to exit infected cells. This highly conserved pathway mediates essential cellular membrane fission events and therefore has limited potential to acquire adaptive mutations to counteract this co-option by viruses. Here, we describe duplicated and truncated copies of the ESCRT-III factor CHMP3 that arose independently in New World monkeys and mice and that block ESCRT-dependent virus budding. When expressed in human cells, these retroCHMP3 proteins potently inhibit the release of retroviruses, paramyxoviruses and filoviruses. RetroCHMP3 proteins have evolved to reduce interactions with other ESCRT-III factors, and to have little effect on cellular ESCRT processes, revealing routes for decoupling cellular ESCRT functions from exploitation by viruses. The repurposing of duplicated ESCRT-III proteins thus provides a mechanism to generate broad-spectrum viral budding inhibitors without disrupting highly conserved essential cellular ESCRT functions.

scholarly journals Current Knowledge and Future Directions for Improving Subsoiling Quality and Reducing Energy Consumption in Conservation Fields

Agriculture ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 575
Author(s):  
Shangyi Lou ◽  
Jin He ◽  
Hongwen Li ◽  
Qingjie Wang ◽  
Caiyun Lu ◽  
...  
Keyword(s):  
Energy Consumption ◽  
Cover Crops ◽  
Current Knowledge ◽  
High Energy ◽  
Field Application ◽  
Research Progress ◽  
Monitoring And Control ◽  
Future Directions ◽  
Tillage Depth ◽  
And Control

Subsoiling has been acknowledged worldwide to break compacted hardpan, improve soil permeability and water storage capacity, and promote topsoil deepening and root growth. However, there exist certain factors which limit the wide in-field application of subsoiling machines. Of these factors, the main two are poor subsoiling quality and high energy consumption, especially the undesired tillage depth obtained in the field with cover crops. Based on the analysis of global adoption and benefits of subsoiling technology, and application status of subsoiling machines, this article reviewed the research methods, technical characteristics, and developing trends in five key aspects, including subsoiling shovel design, anti-drag technologies, technologies of tillage depth detection and control, and research on soil mechanical interaction. Combined with the research progress and application requirements of subsoiling machines across the globe, current problems and technical difficulties were analyzed and summarized. Aiming to solve these problems, improve subsoiling quality, and reduce energy consumption, this article proposed future directions for the development of subsoiling machines, including optimizing the soil model in computer simulation, strengthening research on the subsoiling mechanism and comprehensive effect, developing new tillage depth monitoring and control systems, and improving wear-resisting properties of subsoiling shovels.

scholarly journals A cryo–electron tomography workflow reveals protrusion-mediated shedding on injured plasma membrane

2021 ◽  
Vol 7 (13) ◽  
pp. eabc6345
Author(s):  
Shrawan Kumar Mageswaran ◽  
Wei Yuan Yang ◽  
Yogaditya Chakrabarty ◽  
Catherine M. Oikonomou ◽  
Grant J. Jensen
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Electron Tomography ◽  
Membrane Damage ◽  
Light And Electron Microscopy ◽  
Actin Dynamics ◽  
Endosomal Sorting ◽  
Plasma Membrane Damage ◽  
Cryo Electron Tomography ◽  
Vacuolar Protein

Cryo–electron tomography (cryo-ET) provides structural context to molecular mechanisms underlying biological processes. Although straightforward to implement for studying stable macromolecular complexes, using it to locate short-lived structures and events can be impractical. A combination of live-cell microscopy, correlative light and electron microscopy, and cryo-ET will alleviate this issue. We developed a workflow combining the three to study the ubiquitous and dynamic process of shedding in response to plasma membrane damage in HeLa cells. We found filopodia-like protrusions enriched at damage sites and acting as scaffolds for shedding, which involves F-actin dynamics, myosin-1a, and vacuolar protein sorting 4B (a component of the ‘endosomal sorting complex required for transport’ machinery). Overall, shedding is more complex than current models of vesiculation from flat membranes. Its similarities to constitutive shedding in enterocytes argue for a conserved mechanism. Our workflow can also be adapted to study other damage response pathways and dynamic cellular events.

scholarly journals Phony peach disease: past and present impact on the peach industry in the southeastern U.S.A

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Kendall A. Johnson ◽  
Clive H. Bock ◽  
Phillip M. Brannen
Keyword(s):  
New Technologies ◽  
Current Knowledge ◽  
Future Research ◽  
Management Options ◽  
Disease Epidemiology ◽  
Pathogen Diversity ◽  
Foundational Research ◽  
Global Threat ◽  
And Control ◽  
The Impact

Abstract Background Phony peach disease (PPD) is caused by the plant pathogenic bacterium Xylella fastidiosa subsp. multiplex (Xfm). Historically, the disease has caused severe yield loss in Georgia and elsewhere in the southeastern United States, with millions of PPD trees being removed from peach orchards over the last century. The disease remains a production constraint, and management options are few. Limited research has been conducted on PPD since the 1980s, but the advent of new technologies offers the opportunity for new, foundational research to form a basis for informed management of PPD in the U.S. Furthermore, considering the global threat of Xylella to many plant species, preventing import of Xfm to other regions, particularly where peach is grown, should be considered an important phytosanitary endeavor. Main topics We review PPD, its history and impact on peach production, and the eradication efforts that were conducted for 42 years. Additionally, we review the current knowledge of the pathogen, Xfm, and how that knowledge relates to our understanding of the peach—Xylella pathosystem, including the epidemiology of the disease and consideration of the vectors. Methods used to detect the pathogen in peach are discussed, and ramifications of detection in relation to management and control of PPD are considered. Control options for PPD are limited. Our current knowledge of the pathogen diversity and disease epidemiology are described, and based on this, some potential areas for future research are also considered. Conclusion There is a lack of recent foundational research on PPD and the associated strain of Xfm. More research is needed to reduce the impact of this pathogen on peach production in the southeastern U.S., and, should it spread internationally, wherever peaches are grown.

scholarly journals The role of VPS4 in ESCRT-III polymer remodeling

2019 ◽  
Vol 47 (1) ◽  
pp. 441-448 ◽  
Author(s):  
Christophe Caillat ◽  
Sourav Maity ◽  
Nolwenn Miguet ◽  
Wouter H. Roos ◽  
Winfried Weissenhorn
Keyword(s):  
Active Role ◽  
Mechanistic Models ◽  
Membrane Remodeling ◽  
Filament Formation ◽  
Enveloped Viruses ◽  
Endosomal Sorting ◽  
Membrane Fission ◽  
Dynamic Assembly ◽  
Inside Out

Abstract The endosomal sorting complex required for transport-III (ESCRT-III) and VPS4 catalyze a variety of membrane-remodeling processes in eukaryotes and archaea. Common to these processes is the dynamic recruitment of ESCRT-III proteins from the cytosol to the inner face of a membrane neck structure, their activation and filament formation inside or at the membrane neck and the subsequent or concomitant recruitment of the AAA-type ATPase VPS4. The dynamic assembly of ESCRT-III filaments and VPS4 on cellular membranes induces constriction of membrane necks with large diameters such as the cytokinetic midbody and necks with small diameters such as those of intraluminal vesicles or enveloped viruses. The two processes seem to use different sets of ESCRT-III filaments. Constriction is then thought to set the stage for membrane fission. Here, we review recent progress in understanding the structural transitions of ESCRT-III proteins required for filament formation, the functional role of VPS4 in dynamic ESCRT-III assembly and its active role in filament constriction. The recent data will be discussed in the context of different mechanistic models for inside-out membrane fission.

scholarly journals Severe acute respiratory syndrome (SARS) related coronavirus in bats

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Rong Geng ◽  
Peng Zhou
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Current Knowledge ◽  
Disease Outbreaks ◽  
First Century ◽  
Intermediate Hosts ◽  
Human Coronavirus ◽  
Transmission Potential ◽  
Disease Agent ◽  
And Control ◽  
Genomic Similarity

AbstractThree major human coronavirus disease outbreaks, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and 2019 coronavirus disease (COVID-19), occurred in the twenty-first century and were caused by different coronaviruses (CoVs). All these viruses are considered to have originated from bats and transmitted to humans through intermediate hosts. SARS-CoV-1 and SARS-CoV-2, disease agent of COVID-19, shared around 80% genomic similarity, and thus belong to SARS-related CoVs. As a natural reservoir of viruses, bats harbor numerous other SARS-related CoVs that could potentially infect humans around the world, causing SARS or COVID-19 like outbreaks in the future. In this review, we summarized the current knowledge of CoVs on geographical distribution, genetic diversity, cross-species transmission potential and possible pathogenesis in humans, aiming for a better understanding of bat SARS-related CoVs in the context of prevention and control.

scholarly journals Clinical Progress in Proton Radiotherapy: Biological Unknowns

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 604
Author(s):  
Laura Vanderwaeren ◽  
Rüveyda Dok ◽  
Kevin Verstrepen ◽  
Sandra Nuyts
Keyword(s):  
Proton Irradiation ◽  
Current Knowledge ◽  
Clinical Use ◽  
Proton Radiation ◽  
Photon Irradiation ◽  
Normal Tissues ◽  
The Past ◽  
Depth Dose ◽  
Damage Response ◽  
Depth Dose Distribution

Clinical use of proton radiation has massively increased over the past years. The main reason for this is the beneficial depth-dose distribution of protons that allows to reduce toxicity to normal tissues surrounding the tumor. Despite the experience in the clinical use of protons, the radiobiology after proton irradiation compared to photon irradiation remains to be completely elucidated. Proton radiation may lead to differential damages and activation of biological processes. Here, we will review the current knowledge of proton radiobiology in terms of induction of reactive oxygen species, hypoxia, DNA damage response, as well as cell death after proton irradiation and radioresistance.

scholarly journals Dual Role of Integrin Alpha-6 in Glioblastoma: Supporting Stemness in Proneural Stem-Like Cells While Inducing Radioresistance in Mesenchymal Stem-Like Cells

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3055
Author(s):  
Elisabetta Stanzani ◽  
Leire Pedrosa ◽  
Guillaume Bourmeau ◽  
Oceane Anezo ◽  
Aleix Noguera-Castells ◽  
...  
Keyword(s):  
Cellular Heterogeneity ◽  
In Vitro Assays ◽  
Rna Seq ◽  
Promising Target ◽  
Damage Response ◽  
Integrin Alpha 6 ◽  
And Control ◽  
Improve Patient

Therapeutic resistance after multimodal therapy is the most relevant cause of glioblastoma (GBM) recurrence. Extensive cellular heterogeneity, mainly driven by the presence of GBM stem-like cells (GSCs), strongly correlates with patients’ prognosis and limited response to therapies. Defining the mechanisms that drive stemness and control responsiveness to therapy in a GSC-specific manner is therefore essential. Here we investigated the role of integrin a6 (ITGA6) in controlling stemness and resistance to radiotherapy in proneural and mesenchymal GSCs subtypes. Using cell sorting, gene silencing, RNA-Seq, and in vitro assays, we verified that ITGA6 expression seems crucial for proliferation and stemness of proneural GSCs, while it appears not to be relevant in mesenchymal GSCs under basal conditions. However, when challenged with a fractionated protocol of radiation therapy, comparable to that used in the clinical setting, mesenchymal GSCs were dependent on integrin a6 for survival. Specifically, GSCs with reduced levels of ITGA6 displayed a clear reduction of DNA damage response and perturbation of cell cycle pathways. These data indicate that ITGA6 inhibition is able to overcome the radioresistance of mesenchymal GSCs, while it reduces proliferation and stemness in proneural GSCs. Therefore, integrin a6 controls crucial characteristics across GBM subtypes in GBM heterogeneous biology and thus may represent a promising target to improve patient outcomes.

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