scholarly journals Role of non-motile microtubule-associated proteins in virus trafficking

2016 ◽  
Vol 7 (5-6) ◽  
pp. 283-292 ◽  
Author(s):  
Débora M. Portilho ◽  
Roger Persson ◽  
Nathalie Arhel
Keyword(s):  
Motor Proteins ◽  
Current Knowledge ◽  
Cell Entry ◽  
Cellular Transport ◽  
Microtubule Associated Proteins ◽  
Virus Trafficking ◽  
Cytoskeletal Dynamics ◽  
Associated Proteins ◽  
Infected Cells

AbstractViruses are entirely dependent on their ability to infect a host cell in order to replicate. To reach their site of replication as rapidly and efficiently as possible following cell entry, many have evolved elaborate mechanisms to hijack the cellular transport machinery to propel themselves across the cytoplasm. Long-range movements have been shown to involve motor proteins along microtubules (MTs) and direct interactions between viral proteins and dynein and/or kinesin motors have been well described. Although less well-characterized, it is also becoming increasingly clear that non-motile microtubule-associated proteins (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule plus-end tracking proteins (+TIPs), can also promote viral trafficking in infected cells, by mediating interaction of viruses with filaments and/or motor proteins, and modulating filament stability. Here we review our current knowledge on non-motile MAPs, their role in the regulation of cytoskeletal dynamics and in viral trafficking during the early steps of infection.

scholarly journals Hepatitis C virus cell entry: role of lipoproteins and cellular receptors

2009 ◽  
Vol 90 (5) ◽  
pp. 1055-1070 ◽  
Author(s):  
Michela E. Burlone ◽  
Agata Budkowska
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Current Knowledge ◽  
Scavenger Receptor ◽  
Cell Entry ◽  
Host Cells ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Junction Molecules

Hepatitis C virus (HCV), a major cause of chronic liver disease, is a single-stranded positive sense virus of the family Flaviviridae. HCV cell entry is a multi-step process, involving several viral and cellular factors that trigger virus uptake into the hepatocyte. Tetraspanin CD81, human scavenger receptor SR-BI, and tight junction molecules Claudin-1 and occludin are the main receptors that mediate HCV entry. In addition, the virus may use glycosaminoglycans and/or low density receptors on host cells as initial attachment factors. A unique feature of HCV is the dependence of virus replication and assembly on host cell lipid metabolism. Most notably, during HCV assembly and release from the infected cells, virus particles associate with lipids and very-low-density lipoproteins. Thus, infectious virus circulates in patient sera in the form of triglyceride-rich particles. Consequently, lipoproteins and lipoprotein receptors play an essential role in virus uptake and the initiation of infection. This review summarizes the current knowledge about HCV receptors, mechanisms of HCV cell entry and the role of lipoproteins in this process.

scholarly journals MAP7 recruits kinesin-1 to microtubules to direct organelle transport

2019 ◽  
Author(s):  
Abdullah R. Chaudhary ◽  
Hailong Lu ◽  
Elena B. Krementsova ◽  
Carol S. Bookwalter ◽  
Kathleen M. Trybus ◽  
...  
Keyword(s):  
Single Molecule ◽  
Organelle Transport ◽  
Microtubule Associated Proteins ◽  
Microtubule Polymerization ◽  
Binding Rate ◽  
Associated Proteins ◽  
Bidirectional Transport ◽  
Directed Motility ◽  
Clear Shift

Microtubule-associated proteins (MAPs) play well-characterized roles in regulating microtubule polymerization, dynamics, and organization. In addition, MAPs control trans-port along microtubules by regulating the motility of kinesin and dynein. MAP7 (ensconsin, E-MAP-115) is a ubiquitous MAP that organizes the microtubule cytoskeleton in mitosis and neuronal branching. MAP7 also promotes the interaction of kinesin-1 with microtubules. We expressed and purified full-length kinesin-1 and MAP7 in Sf9 cells. In single-molecule motiity assays, MAP7 recruits kinesin-1 to microtubules, increasing the frequency of both diffusive and processive runs. Optical trapping assays on beads transported by single and teams of kinesin-1 motors indicate that MAP7 increases the relative binding rate of kinesin-1 and the number of motors simultaneously engaged in ensembles. To examine the role of MAP7 in regulating bidirectional transport, we isolated late phagosomes along with their native set of kinesin-1, kinesin-2, and dynein motors. Bidirectional cargoes exhibit a clear shift towards plus-end directed motility on MAP7-decorated microtubules due to increased forces exerted by kinesin teams. Collectively, our results indicate that MAP7 enhances kinesin-1 recruitment to microtubules and targets organelle transport to the plus end.

scholarly journals Neutrophil Involvement in Covid-19

2020 ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Interaction Network ◽  
Lavage Fluid ◽  
Lung Epithelial Cells ◽  
Organ Injury ◽  
Rna Seq ◽  
Protein Protein Interaction ◽  
Associated Proteins ◽  
Infected Cells ◽  
Neutrophil Response

Covid-19 is often related to hyperinflammation that drives lung or multi-organ injury. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational protein-protein interaction network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated proteins, led to the mining of a robust neutrophil response signature and multiple relevant inflammatory genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 revealed that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. Third, analysis of RNA-seq datasets of bronchoalveolar lavage fluid from Covid-19 patients, identified neutrophil-specific genes and chemokines. Different immunoregulatory and neutrophil-relevant molecules mined here such as, TNFR, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP and LAP3 are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases. The role of neutrophils in Covid-19 needs to be studied further.

Role of ATP-binding Cassette Transporters in Sorafenib Therapy for Hepatocellular Carcinoma: an overview

2021 ◽  
Vol 22 ◽  
Author(s):  
Maria Manuela Estevinho ◽  
Carlos Fernandes ◽  
João Carlos Silva ◽  
Ana Catarina Gomes ◽  
Edgar Afecto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multidrug Resistance ◽  
Abc Transporters ◽  
Current Knowledge ◽  
Molecular Therapy ◽  
Resistance Factors ◽  
Sorafenib Therapy ◽  
Online Databases ◽  
Associated Proteins

Background: Molecular therapy with sorafenib remains the mainstay for advanced-stage hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining long-lasting benefits due to the high chemoresistance rate. Objective: To perform, for the first time, an overview of the literature concerning the role of adenosine triphosphate-binding cassette (ABC) transporters in sorafenib therapy for hepatocellular carcinoma. Methods: Three online databases (PubMed, Web of Science and Scopus) were searched, from inception to October 2020. Studies selection, analysis and data collection was independently performed by two authors. Results: The search yielded 224 results; 29 were selected for inclusion. Most studies were pre-clinical, using HCC cell lines; three used human samples. Studies highlight the effect of sorafenib in decreasing ABC transporters expression. Conversely, it is described the role of ABC transporters, particularly multidrug resistance protein 1 (MDR-1), multidrug resistance-associated proteins 1 and 2 (MRP-1 and MRP-2) and ABC subfamily G member 2 (ABCG2) in sorafenib pharmacokinetics and pharmacodynamics, being key resistance factors. Combination therapy with naturally available or synthetic compounds that modulate ABC transporters may revert sorafenib resistance, by increasing absorption and intracellular concentration. Conclusion: A deeper understanding of ABC transporters’ mechanisms may provide guidance for developing innovative approaches for hepatocellular carcinoma. Further studies are warranted to translate the current knowledge into practice and paving the way to individualized therapy.

scholarly journals Role of MAP1B in axonal retrograde transport of mitochondria

2006 ◽  
Vol 397 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Eva-María Jiménez-Mateos ◽  
Christian González-Billault ◽  
Hana N. Dawson ◽  
Michael P. Vitek ◽  
Jesús Avila
Keyword(s):  
Axonal Transport ◽  
Retrograde Transport ◽  
Precise Control ◽  
Microtubule Associated Proteins ◽  
Anterograde Axonal Transport ◽  
Associated Proteins ◽  
Regulation Of Transport ◽  
The Stability ◽  
Additional Role

The MAPs (microtubule-associated proteins) MAP1B and tau are well known for binding to microtubules and stabilizing these structures. An additional role for MAPs has emerged recently where they appear to participate in the regulation of transport of cargos on the microtubules found in axons. In this role, tau has been associated with the regulation of anterograde axonal transport. We now report that MAP1B is associated with the regulation of retrograde axonal transport of mitochondria. This finding potentially provides precise control of axonal transport by MAPs at several levels: controlling the anterograde or retrograde direction of transport depending on the type of MAP involved, controlling the speed of transport and controlling the stability of the microtubule tracks upon which transport occurs.

scholarly journals Organization of DNA in Mammalian Mitochondria

2019 ◽  
Vol 20 (11) ◽  
pp. 2770 ◽  
Author(s):  
Géraldine Farge ◽  
Maria Falkenberg
Keyword(s):  
Single Molecule ◽  
Current Knowledge ◽  
Autonomously Replicating Sequence ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Nucleoids ◽  
Associated Proteins ◽  
A Cell ◽  
Mtdna Replication ◽  
Mitochondrial Transcription Factor A

As with all organisms that must organize and condense their DNA to fit within the limited volume of a cell or a nucleus, mammalian mitochondrial DNA (mtDNA) is packaged into nucleoprotein structures called nucleoids. In this study, we first introduce the general modes of DNA compaction, especially the role of the nucleoid-associated proteins (NAPs) that structure the bacterial chromosome. We then present the mitochondrial nucleoid and the main factors responsible for packaging of mtDNA: ARS- (autonomously replicating sequence-) binding factor 2 protein (Abf2p) in yeast and mitochondrial transcription factor A (TFAM) in mammals. We summarize the single-molecule manipulation experiments on mtDNA compaction and visualization of mitochondrial nucleoids that have led to our current knowledge on mtDNA compaction. Lastly, we discuss the possible regulatory role of DNA packaging by TFAM in DNA transactions such as mtDNA replication and transcription.

scholarly journals The Role of Extracellular Vesicles in Viral Infection and Transmission

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 102 ◽  
Author(s):  
Lorena Urbanelli ◽  
Sandra Buratta ◽  
Brunella Tancini ◽  
Krizia Sagini ◽  
Federica Delo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Extracellular Vesicles ◽  
Secretory Pathway ◽  
Cell Entry ◽  
Host Factors ◽  
Intercellular Signaling ◽  
Viral Pathogens ◽  
Infected Cells

Extracellular vesicles (EVs) have been found to be released by any type of cell and can be retrieved in every circulating body fluid, namely blood (plasma, serum), saliva, milk, and urine. EVs were initially considered a cellular garbage disposal tool, but later it became evident that they are involved in intercellular signaling. There is evidence that viruses can use EV endocytic routes to enter uninfected cells and hijack the EV secretory pathway to exit infected cells, thus illustrating that EVs and viruses share common cell entry and biogenesis mechanisms. Moreover, EVs play a role in immune response against viral pathogens. EVs incorporate and spread both viral and host factors, thereby prompting or inhibiting immune responses towards them via a multiplicity of mechanisms. The involvement of EVs in immune responses, and their potential use as agents modulating viral infection, will be examined. Although further studies are needed, the engineering of EVs could package viral elements or host factors selected for their immunostimulatory properties, to be used as vaccines or tolerogenic tools in autoimmune diseases.

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