scholarly journals Different temporal requirements for the LRR transmembrane receptors Tartan and Toll-2 in the formation of contractile interfaces at compartmental boundaries

2021 ◽  
Author(s):  
Thomas E Sharrock ◽  
Guy B Blanchard ◽  
Jenny Evans ◽  
Bénédicte Sanson
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Real Time ◽  
The Body ◽  
Germ Band ◽  
Transmembrane Receptors ◽  
Physical Separation ◽  
Surface Receptors ◽  
Boundary Cell ◽  
Drosophila Embryos

Compartmental boundaries physically separate groups of epithelial cells, a property fundamental for the organization of the body plan in both insects and vertebrates. In many examples, this physical separation has been shown to be the consequence of a regulated increase in contractility of the actomyosin cortex at boundary cell-cell interfaces, a property important in developmental morphogenesis beyond compartmental boundary formation. In this study, we took an unbiased screening approach to identify cell surface receptors required for actomyosin enrichment and polarisation at parasegmental boundaries (PSBs) in early Drosophila embryos, leading us to uncover different temporal requirements for two LRR receptors, Tartan and Toll-2. First, we find that Tartan is required during germband extension for actomyosin enrichment at PSBs, confirming an earlier report. Next, by following in real time the dynamics of loss of boundary straightness in tartan mutant embryos compared to wildtype and ftz mutant embryos, we show that Tartan is not required beyond germband extension. At this stage, actomyosin enrichment at PSBs becomes regulated by Wingless signalling. We find that Wingless signalling regulates Toll-2 expression and we show that Toll-2 is required for planar polarization of actomyosin after the completion of germ-band extension. Thus the formation of contractile interfaces at PSBs depends on a dynamic set of LRR receptors cues. Our study also suggests that the number of receptor cues is small and that the receptors are interchangeable.

scholarly journals Insulin’s Discovery: New Insights on Its Hundredth Birthday: From Insulin Action and Clearance to Sweet Networks

2021 ◽  
Vol 22 (3) ◽  
pp. 1030
Author(s):  
Melanie Leroux ◽  
Martial Boutchueng-Djidjou ◽  
Robert Faure
Keyword(s):  
Type 1 Diabetes ◽  
Cell Surface ◽  
20Th Century ◽  
Insulin Action ◽  
100Th Anniversary ◽  
The Body ◽  
Nobel Lecture ◽  
Surface Receptors ◽  
The Third

In 2021, the 100th anniversary of the isolation of insulin and the rescue of a child with type 1 diabetes from death will be marked. In this review, we highlight advances since the ingenious work of the four discoverers, Frederick Grant Banting, John James Rickard Macleod, James Bertram Collip and Charles Herbert Best. Macleoad closed his Nobel Lecture speech by raising the question of the mechanism of insulin action in the body. This challenge attracted many investigators, and the question remained unanswered until the third part of the 20th century. We summarize what has been learned, from the discovery of cell surface receptors, insulin action, and clearance, to network and precision medicine.

scholarly journals Dynamic Monitoring of Cell Adhesion and Spreading on Microelectronic Sensor Arrays

2005 ◽  
Vol 10 (8) ◽  
pp. 795-805 ◽  
Author(s):  
Josephine M. Atienza ◽  
Jenny Zhu ◽  
Xiaobo Wang ◽  
Xiao Xu ◽  
Yama Abassi
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Real Time ◽  
Specific Interaction ◽  
Sensor Arrays ◽  
Dynamic Monitoring ◽  
Cellular Interaction ◽  
Cell Surface Receptors ◽  
Label Free ◽  
Surface Receptors

Cellular interaction with and adhesion on different biological surfaces is a dynamic and integrated process requiring the participation of specialized cell surface receptors, structural proteins, signaling proteins, and the cellular cytoskeleton. In this report, the authors describe a label-free and real-time method for measuring and monitoring cell adhesion on special microplates integrated with electronic cell sensor arrays. These plates were used in conjunction with the real-time cell electronic sensing (RT-CES™) system to dynamically and quantitatively monitor the specific interaction of fibroblasts with extracellular matrix (ECM) proteins and compared with standard adhesion techniques. Cell adhesion on ECM-coated cell sensor arrays is dependent on the concentration of ECMproteins coated and is inhibited by agents that disrupt the interaction of ECM with cell surface receptors. Furthermore, the authors demonstrate that the integrity of the actin cytoskeleton is required for productive cell adhesion and spreading on ECM-coated microelectronic sensors. Confirming earlier results, it is shown that interfering with Src expression or activity, via siRNA or small molecule, results in the disruption of adhesion and spreading of Bx PC3cells. The results indicate that the RT-CES system offers a convenient and quantitative means of assessing the kinetics of cell adhesion in a high-throughput manner.

scholarly journals May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression

2022 ◽  
Vol 9 ◽  
Author(s):  
Donnell L. Williams ◽  
Veronica Maria Sikora ◽  
Max A. Hammer ◽  
Sayali Amin ◽  
Taema Brinjikji ◽  
...  
Keyword(s):  
Cell Surface ◽  
Molecular Mechanisms ◽  
Antigenic Variation ◽  
The Body ◽  
Allelic Exclusion ◽  
Coat Proteins ◽  
Cell Surface Molecule ◽  
Strand Breaks ◽  
Surface Receptors ◽  
Molecular Noise

How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.

scholarly journals SNAPS: A toolkit for studying cell surface shedding of diverse transmembrane receptors

2018 ◽  
Author(s):  
Amanda N. Hayward ◽  
Eric J. Aird ◽  
Wendy R. Gordon
Keyword(s):  
Cell Surface ◽  
Cellular Communication ◽  
Structural Homology ◽  
Transmembrane Receptors ◽  
Surface Receptors ◽  
Communication Mechanism ◽  
Regulation Mechanisms ◽  
Input Response ◽  
Potential Therapeutics ◽  
Screen Surface

SummaryProteolysis of transmembrane receptors is a critical cellular communication mechanism dysregulated in many diseases, yet decoding proteolytic regulation mechanisms of the estimated 400 receptors shed from the cell surface has been hindered by difficulties in controlling stimuli and unknown fates of cleavage products. Notch proteolytic regulation is a notable exception, where decades of study have revealed that intercellular forces drive exposure of a cryptic protease site within a juxtamembrane “proteolytic switch” domain to activate transcriptional programs inside the cell. Thus, we created a Synthetic Notch Assay for Proteolytic Switches (SNAPS) that exploits the modularity and unequivocal input/response of Notch proteolysis to screen surface receptors for other putative proteolytic switches. Here, we identify several new proteolytic switches among receptors with structural homology to Notch. We demonstrate that SNAPS can detect shedding in chimeras of diverse cell surface receptors, leading to new, testable hypotheses. Finally, we establish that the assay can be used to measure modulation of proteolysis by potential therapeutics.

scholarly journals Anthrax Toxin Entry into Polarized Epithelial Cells

1999 ◽  
Vol 67 (6) ◽  
pp. 3026-3030 ◽  
Author(s):  
Kathryn E. Beauregard ◽  
Susan Wimer-Mackin ◽  
R. John Collier ◽  
Wayne I. Lencer
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Protective Antigen ◽  
Basolateral Membrane ◽  
Anthrax Toxin ◽  
Apical Surface ◽  
T84 Cells ◽  
Surface Receptors ◽  
Edema Factor ◽  
Edema Toxin

ABSTRACT We examined the entry of anthrax edema toxin (EdTx) into polarized human T84 epithelial cells using cyclic AMP-regulated Cl−secretion as an index of toxin entry. EdTx is a binary A/B toxin which self assembles at the cell surface from anthrax edema factor and protective antigen (PA). PA binds to cell surface receptors and delivers EF, an adenylate cyclase, to the cytosol. EdTx elicited a strong Cl− secretory response when it was applied to the basolateral surface of T84 cells but no response when it was applied to the apical surface. PA alone had no effect when it was applied to either surface. T84 cells exposed basolaterally bound at least 30-fold-more PA than did T84 cells exposed apically, indicating that the PA receptor is largely or completely restricted to the basolateral membrane of these cells. The PA receptor did not fractionate with detergent-insoluble caveola-like membranes as cholera toxin receptors do. These findings have implications regarding the nature of the PA receptor and confirm the view that EdTx and CT coopt fundamentally different subcellular systems to enter the cell and cause disease.

scholarly journals A toolkit for studying cell surface shedding of diverse transmembrane receptors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Amanda N Hayward ◽  
Eric J Aird ◽  
Wendy R Gordon
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Cellular Communication ◽  
Structural Homology ◽  
Transmembrane Receptors ◽  
Surface Receptors ◽  
Regulation Mechanisms ◽  
Input Response ◽  
Potential Therapeutics ◽  
Screen Surface

Proteolysis of transmembrane receptors is a critical cellular communication mechanism dysregulated in disease, yet decoding proteolytic regulation mechanisms of hundreds of shed receptors is hindered by difficulties controlling stimuli and unknown fates of cleavage products. Notch proteolytic regulation is a notable exception, where intercellular forces drive exposure of a cryptic protease site within a juxtamembrane proteolytic switch domain to activate transcriptional programs. We created a Synthetic Notch Assay for Proteolytic Switches (SNAPS) that exploits the modularity and unequivocal input/response of Notch proteolysis to screen surface receptors for other putative proteolytic switches. We identify several new proteolytic switches among receptors with structural homology to Notch. We demonstrate SNAPS can detect shedding in chimeras of diverse cell surface receptors, leading to new, testable hypotheses. Finally, we establish the assay can be used to measure modulation of proteolysis by potential therapeutics and offer new mechanistic insights into how DECMA-1 disrupts cell adhesion.

scholarly journals The Human Cytomegalovirus Trimer and Pentamer Promote Sequential Steps in Entry into Epithelial and Endothelial Cells at Cell Surfaces and Endosomes

2018 ◽  
Vol 92 (21) ◽  
Author(s):  
Jing Liu ◽  
Ted S. Jardetzky ◽  
Andrea L. Chin ◽  
David C. Johnson ◽  
Adam L. Vanarsdall
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Human Cytomegalovirus ◽  
Antiviral Agents ◽  
Cell Types ◽  
Surface Binding ◽  
Surface Receptors ◽  
Virus Particles ◽  
Early Endosomes

ABSTRACTHuman cytomegalovirus (HCMV) infects a wide variety of human cell types by different entry pathways that involve distinct envelope glycoprotein complexes that include gH/gL, a trimer complex consisting of gHgL/gO, and a pentamer complex consisting of gH/gL/UL128/UL130/UL131. We characterized the effects of soluble forms of these proteins on HCMV entry. Soluble trimer and pentamer blocked entry of HCMV into epithelial and endothelial cells, whereas soluble gH/gL did not. Trimer inhibited HCMV entry into fibroblast cells, but pentamer and gH/gL did not. Both trimer and pentamer bound to the surfaces of fibroblasts and epithelial cells, whereas gH/gL did not bind to either cell type. Cell surface binding of trimer and pentamer did not involve heparin sulfate moieties. The ability of soluble trimer to block entry of HCMV into epithelial cells did not involve platelet-derived growth factor PDGFRα, which has been reported as a trimer receptor for fibroblasts. Soluble trimer reduced the amount of virus particles that could be adsorbed onto the surface of epithelial cells, whereas soluble pentamer had no effect on virus adsorption. However, soluble pentamer reduced the ability of virus particles to exit from early endosomes into the cytoplasm and then travel to the nucleus. These studies support a model in which both the trimer and pentamer are required for HCMV entry into epithelial and endothelial cells, with trimer interacting with cell surface receptors other than PDGFR and pentamer acting later in the entry pathway to promote egress from endosomes.IMPORTANCEHCMV infects nearly 80% of the world's population and causes significant morbidity and mortality. The current antiviral agents used to treat HCMV infections are prone to resistance and can be toxic to patients, and there is no current vaccine against HCMV available. The data in this report will lead to a better understanding of how essential HCMV envelope glycoproteins function during infection of biologically important cell types and will have significant implications for understanding HCMV pathogenesis for developing new therapeutics.

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