scholarly journals Computational Characterization of the mtORF of Pocilloporid Corals: Insights into Differences in Protein Structure and Function among Stylophora Lineages from Contrasting Environments

2019 ◽  
Author(s):  
Eulalia Banguera-Hinestroza ◽  
Yvonne Sawall ◽  
Jean-François Flot
Keyword(s):  
Stress Response ◽  
Transmembrane Protein ◽  
Thermal Adaptation ◽  
Cell Surface Receptor ◽  
Reading Frame ◽  
Intrinsically Disordered ◽  
Protein Functions ◽  
Surface Receptor ◽  
Environmental Variations ◽  
And Function

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae, which turn out to be an effective barcode gene for these corals. However, its function remains unknown. Recently, this gene revealed the existence of a hybrid Stylophora lineage (RS_LinA) inhabiting in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C) with its parental species (RS_LinB). Furthermore, in RS_LinB, the mtORF uncovered phylogeographic patterns that were strongly correlated with environmental variations. This was similar to the patterns unraveled by hsp70, suggesting that mtORF too might be involved in thermal adaptation. Here we used computational approaches to characterize the mtORF and to identify its potential role. Results showed that this gene encodes a transmembrane protein (0.97<P< 1.00) involved in transport (0.80<P< 0.87), regulation of metabolic processes (0.70<P<0.85), and likely in the cell-surface receptor signaling pathway (0.56<P<0.80). Predicted protein functions differed among Stylophora lineages and interestingly, in RS_LinB only, the protein was intrinsically disordered and displayed domains involved in cellular complexes and stress response (0.0001< P <0.001). These characteristics, exclusive of an endemic lineage adapted to extreme environmental fluctuations, support a role of the mtORF in stress response, speciation and adaptation.

scholarly journals Sustained TREM2 stabilization accelerates microglia heterogeneity and Abeta pathology in a mouse model of Alzheimer s disease

2021 ◽  
Author(s):  
Rahul Dhandapani ◽  
Marilisa Neri ◽  
Mario Bernhard ◽  
Irena Brzak ◽  
Tatjana Schweizer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Proteolytic Cleavage ◽  
Cell Surface Receptor ◽  
Pathological Conditions ◽  
Mouse Cortex ◽  
Surface Receptor ◽  
And Function ◽  
The Brain

TREM2 is a transmembrane protein expressed exclusively in microglia in the brain that regulates inflammatory responses to pathological conditions. Proteolytic cleavage of membrane TREM2 affects microglial function and is associated with Alzheimer s disease, but the consequence of reduced TREM2 proteolytic cleavage has not been determined. We generated a transgenic mouse model of reduced TREM2 shedding (Trem2-IPD) through amino acid substitution of ADAM-protease recognition site. We found that Trem2-IPD mice displayed increased TREM2 cell surface receptor load, survival and function in myeloid cells. Using single cell transcriptomic profiling of mouse cortex we show that sustained TREM2 stabilization induces a shift of fate in microglial maturation and accelerates microglial responses to Abeta pathology in a mouse model of Alzheimer s disease. Our data indicate that reduction of TREM2 proteolytic cleavage aggravates neuroinflammation during the course of AD pathology suggesting that TREM2 shedding is a critical regulator of microglial activity in pathological states.

scholarly journals Correlated STORM-homoFRET Imaging: Applications to the Study of Membrane Receptor Self-Association and Clustering

2021 ◽  
Author(s):  
Amine Driouchi ◽  
Scott Gray-Owen ◽  
Christopher M Yip
Keyword(s):  
Spatial Distribution ◽  
Membrane Proteins ◽  
Complex Mixture ◽  
Cell Surface Receptor ◽  
Oligomeric State ◽  
Imaging Approach ◽  
Surface Receptor ◽  
A Cell ◽  
Self Association ◽  
And Function

Mapping the self-organization and spatial distribution of membrane proteins is key to understanding their function. We report here on a correlated STORM/homoFRET imaging approach for resolving the nanoscale distribution and oligomeric state of membrane proteins. Live cell homoFRET imaging of CEACAM1, a cell-surface receptor known to exist in a complex equilibrium between monomer and dimer/oligomer states, revealed highly heterogenous diffraction-limited structures on the surface of HeLa cells. Correlated super-resolved STORM imaging revealed that these structures comprised a complex mixture and spatial distribution of self-associated CEACAM1 molecules. This correlated approach provides a compelling strategy for addressing challenging questions about the interplay between membrane protein concentration, distribution, interaction, clustering, and function.

scholarly journals Stimulatory Effects of Peroxisome Proliferator-Activated Receptor-γon FcγReceptor-Mediated Phagocytosis by Alveolar Macrophages

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-8 ◽  
Author(s):  
David M. Aronoff ◽  
Carlos H. Serezani ◽  
Jennifer K. Carstens ◽  
Teresa Marshall ◽  
Srinivasa R. Gangireddy ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Peritoneal Macrophages ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Peroxisome Proliferator ◽  
Quiescent State ◽  
Peroxisome Proliferator Activated Receptor ◽  
Downstream Signaling ◽  
Surface Receptor ◽  
And Function

Alveolar macrophages abundantly express PPAR-γ, with both natural and synthetic agonists maintaining the cell in a quiescent state hyporesponsive to antigen stimulation. Conversely, agonists upregulate expression and function of the cell-surface receptor CD36, which mediates phagocytosis of lipids, apoptotic neutrophils, and other unopsonized materials. These effects led us to investigate the actions of PPAR-γagonists on the Fcγreceptor, which mediates phagocytosis of particles opsonized by binding of immunoglobulin G antibodies. We found that troglitazone, rosiglitazone, and 15-deoxy-Δ12,14-prostaglandinJ2increase the ability of alveolar, but not peritoneal, macrophages to carry out phagocytosis mediated by the Fcγreceptor. Receptor expression was not altered but activation of the downstream signaling proteins Syk, ERK-1, and ERK-2 was observed. Although it was previously known that PPAR-γligands stimulate phagocytosis of unopsonized materials, this is the first demonstration that they stimulate phagocytosis of opsonized materials as well.

scholarly journals Neutrophil and monocyte dysfunctional effector response towards bacterial challenge in critically-ill COVID-19 patients

2020 ◽  
Author(s):  
Srikanth Mairpady Shambat ◽  
Alejandro Gómez-Mejia ◽  
Tiziano A. Schweizer ◽  
Markus Huemer ◽  
Chun-Chi Chang ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Distinct Pattern ◽  
Innate Immune ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Functional Responses ◽  
Innate Immune Signaling ◽  
Surface Receptor ◽  
And Function ◽  
Effector Response

AbstractCOVID-19 displays diverse disease severities and symptoms. Elevated inflammation mediated by hypercytokinemia induces a detrimental dysregulation of immune cells. However, there is limited understanding of how SARS-CoV-2 pathogenesis impedes innate immune signaling and function against secondary bacterial infections. We assessed the influence of COVID-19 hypercytokinemia on the functional responses of neutrophils and monocytes upon bacterial challenges from acute and corresponding recovery COVID-19 ICU patients. We show that severe hypercytokinemia in COVID-19 patients correlated with bacterial superinfections. Neutrophils and monocytes from acute COVID-19 patients showed severely impaired microbicidal capacity, reflected by abrogated ROS and MPO production as well as reduced NETs upon bacterial challenges. We observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes leading to a suppressive autocrine and paracrine signaling during bacterial challenges. Our data provide insights into the innate immune status of COVID-19 patients mediated by their hypercytokinemia and its transient effect on immune dysregulation upon subsequent bacterial infections

scholarly journals Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 2836 ◽  
Author(s):  
Grace Mallett ◽  
Arian Laurence ◽  
Shoba Amarnath
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Surface Receptor ◽  
Programmed Cell Death 1 ◽  
Surface Receptor ◽  
A Cell ◽  
And Function

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.

scholarly journals Computational Characterization of the mtORF of Pocilloporid Corals: Insights into Protein Structure and Function in Stylophora Lineages from Contrasting Environments

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 324
Author(s):  
Banguera-Hinestroza ◽  
Ferrada ◽  
Sawall ◽  
Flot
Keyword(s):  
Red Sea ◽  
Metal Binding ◽  
Tandem Repeats ◽  
Environmental Changes ◽  
Transmembrane Protein ◽  
Domain Architecture ◽  
Thermal Adaptation ◽  
Functional Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae and has been used since then as an effective barcode for these corals. Recently, mtORF sequencing revealed the existence of two differentiated Stylophora lineages occurring in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C). In the endemic Red Sea lineage RS_LinB, the mtORF and the heat shock protein gene hsp70 uncovered similar phylogeographic patterns strongly correlated with environmental variations. This suggests that the mtORF too might be involved in thermal adaptation. Here, we used computational analyses to explore the features and putative function of this mtORF. In particular, we tested the likelihood that this gene encodes a functional protein and whether it may play a role in adaptation. Analyses of full mitogenomes showed that the mtORF originated in the common ancestor of Madracis and other pocilloporids, and that it encodes a transmembrane protein differing in length and domain architecture among genera. Homology-based annotation and the relative conservation of metal-binding sites revealed traces of an ancient hydrolase catalytic activity. Furthermore, signals of pervasive purifying selection, lack of stop codons in 1830 sequences analyzed, and a codon-usage bias similar to that of other mitochondrial genes indicate that the protein is functional, i.e., not a pseudogene. Other features, such as intrinsically disordered regions, tandem repeats, and signals of positive selection particularly in Stylophora RS_LinB populations, are consistent with a role of the mtORF in adaptive responses to environmental changes.

Ligand Binding to the Cell-Surface Receptor for Reovirus Type 3 Alters Schwann Cell Growth and Function

1990 ◽  
Vol 605 (1 Myelination a) ◽  
pp. 412-415
Author(s):  
JEFFREY A. COHEN ◽  
WILLIAM V. WILLIAMS ◽  
KENNETH F. MORE ◽  
HARISH SEHDEV ◽  
JAMES G. DAVIES ◽  
...  
Keyword(s):  
Cell Growth ◽  
Schwann Cell ◽  
Cell Surface ◽  
Ligand Binding ◽  
Cell Surface Receptor ◽  
Reovirus Type ◽  
Surface Receptor ◽  
And Function ◽  
Type 3

scholarly journals Expression levels of functional folate receptors α and β are related to the number of N-glycosylated sites

1997 ◽  
Vol 327 (3) ◽  
pp. 759-764 ◽  
Author(s):  
Feng SHEN ◽  
Huiquan WANG ◽  
Xuan ZHENG ◽  
Manohar RATNAM
Keyword(s):  
Folic Acid ◽  
Cell Surface ◽  
Folate Receptor ◽  
Glycosylation Site ◽  
Cell Surface Receptor ◽  
Wild Type ◽  
Mutant Proteins ◽  
Surface Receptor ◽  
And Function

In a previous study with inhibitors of N-glycosylation, it was proposed that core glycosylation of the folate receptor (FR) is required for the proper folding of the protein [Luhrs (1991) Blood 77, 1171-1180]. The human FR isoforms type α and type β have three and two candidate sites for N-glycosylation respectively, only one of which is conserved. The significance of N-glycosylation at each of these loci in the expression and function of FR was examined by eliminating the sites both individually and in combination by introducing Asn → Gln substitutions. Translation experiments in vitro showed that the mutations did not alter the synthetic rates of the polypeptides. The recombinant proteins were expressed in human 293 fibroblasts. Treatment with N-glycanase and analysis by Western blotting of the wild-type and mutant proteins revealed that all of the candidate sites in both FR-α and FR-β are glycosylated. When all of the N-glycosylation sites were abolished, 2% and 8% of FR-α and FR-β respectively were expressed on the cell surface compared with the corresponding wild-type proteins; the residual FR polypeptides in the cell lysates were unable to bind [3H]folic acid. In both the proteins, the inclusion of each additional N-glycosylation site partly contributed to restoration of cell surface [3H]folic acid binding and receptor-mediated folate transport. Further, in FR-β the introduction of an additional unnatural site of N-glycosylation resulted in the enhancement of the expression of the cell surface receptor compared with the wild-type protein. The results indicate that the total mass of N-glycosylation, not a specific locus of the modification, is critical for the efficient folding and optimal expression of functional FR-α and FR-β.

scholarly journals The evolution of protein domain families

2009 ◽  
Vol 37 (4) ◽  
pp. 751-755 ◽  
Author(s):  
Marija Buljan ◽  
Alex Bateman
Keyword(s):  
Domain Architecture ◽  
Protein Domains ◽  
Protein Domain ◽  
Cell Surface Receptor ◽  
Immunoglobulin Superfamily ◽  
Insertion And Deletion ◽  
Variable Domains ◽  
Surface Receptor ◽  
Duplication Events ◽  
And Function

Protein domains are the common currency of protein structure and function. Over 10000 such protein families have now been collected in the Pfam database. Using these data along with animal gene phylogenies from TreeFam allowed us to investigate the gain and loss of protein domains. Most gains and losses of domains occur at protein termini. We show that the nature of changes is similar after speciation or duplication events. However, changes in domain architecture happen at a higher frequency after gene duplication. We suggest that the bias towards protein termini is largely because insertion and deletion of domains at most positions in a protein are likely to disrupt the structure of existing domains. We can also use Pfam to trace the evolution of specific families. For example, the immunoglobulin superfamily can be traced over 500 million years during its expansion into one of the largest families in the human genome. It can be shown that this protein family has its origins in basic animals such as the poriferan sponges where it is found in cell-surface-receptor proteins. We can trace how the structure and sequence of this family diverged during vertebrate evolution into constant and variable domains that are found in the antibodies of our immune system as well as in neural and muscle proteins.

scholarly journals Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 575-584 ◽  
Author(s):  
Manik C. Ghosh ◽  
Dolgor Baatar ◽  
Gary Collins ◽  
Arnell Carter ◽  
Fred Indig ◽  
...  
Keyword(s):  
T Cells ◽  
Actin Polymerization ◽  
Cell Types ◽  
Cell Surface Receptor ◽  
Kinase Activation ◽  
Disease States ◽  
Chemokine Signaling ◽  
Human T Cells ◽  
Surface Receptor ◽  
And Function

Abstract Dexamethasone (DM) is a synthetic member of the glucocorticoid (GC) class of hormones that possesses anti-inflammatory and immunosuppressant activity and is commonly used to treat chronic inflammatory disorders, severe allergies, and other disease states. Although GCs are known to mediate well-defined transcriptional effects via GC receptors (GCR), there is increasing evidence that GCs also initiate rapid nongenomic signaling events in a variety of cell types. Here, we report that DM induces the phosphorylation of Lck and the activation of other downstream mediators, including p59Fyn, Zap70, Rac1, and Vav in resting but not activated human T cells. DM treatment also augments CXCL12-mediated signaling in resting T cells through its cell surface receptor, CXCR4 resulting in the enhanced actin polymerization, Rac activation, and cell migration on ligand exposure. Lck was found to be a critical intermediate in these DM-induced signaling activities. Moreover, DM-mediated Lck phosphorylation in T cells was dependent on the presence of both the GCR and the CD45 molecule. Overall, these results elucidate additional nongenomic effects of DM and the GCR on resting human T cells, inducing Lck and downstream kinase activation and augmenting chemokine signaling and function.

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