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 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 Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Pietro Poggio ◽  
Matteo Sorge ◽  
Laura Seclì ◽  
Mara Brancaccio
Keyword(s):  
Tumor Microenvironment ◽  
Cell Surface ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Diagnostic Tools ◽  
Surface Receptors ◽  
And Behavior ◽  
Cancer Cell Signaling ◽  
The Impact ◽  
Stimulation Of

HSP90 is released by cancer cells in the tumor microenvironment where it associates with different co-chaperones generating complexes with specific functions, ranging from folding and activation of extracellular clients to the stimulation of cell surface receptors. Emerging data indicate that these functions are essential for tumor growth and progression. The understanding of the exact composition of extracellular HSP90 complexes and the molecular mechanisms at the basis of their functions in the tumor microenvironment may represent the first step to design innovative diagnostic tools and new effective therapies. Here we review the impact of extracellular HSP90 complexes on cancer cell signaling and behavior.

scholarly journals The c-Met receptor: Implication for targeted therapies in colorectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769911 ◽  
Author(s):  
Elmira Safaie Qamsari ◽  
Sepideh Safaei Ghaderi ◽  
Bahareh Zarei ◽  
Ruhollah Dorostkar ◽  
Salman Bagheri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Surface ◽  
Tyrosine Kinase ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tumor Formation ◽  
Surface Proteins ◽  
Tyrosine Kinase Receptor ◽  
Met Receptor ◽  
Surface Receptors

c-Met (mesenchymal–epithelial transition factor) is a tyrosine kinase receptor activated by hepatocyte growth factor and regulates multiple biological processes, such as cell scattering, survival, and proliferation. Aberrant c-Met signaling has been implicated in a variety of cancer types, including colorectal cancer. c-Met is genetically altered through various mechanisms that is associated with colorectal cancer progression and metastasis. Especially, in colorectal cancer, preclinical evidence for the aberrant activation of the c-Met signaling exists. Accordingly, molecular targeting of c-Met receptor could be a promising strategy, in the treatment of colorectal cancer patients. Recently, it was also shown that crosstalk between c-Met and other cell surface receptors attributes to tumorigenesis and development of therapeutic resistance. Characterization of the molecular mechanisms through which c-Met crosstalks with other receptors in favor of tumor formation and progression remains to explore. This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer. Novel therapeutic approaches for c-Met pathway targeting will also be discussed.

scholarly journals Expression cloning of a human Fc receptor for IgA.

1990 ◽  
Vol 172 (6) ◽  
pp. 1665-1672 ◽  
Author(s):  
C R Maliszewski ◽  
C J March ◽  
M A Schoenborn ◽  
S Gimpel ◽  
L Shen
Keyword(s):  
Cell Surface ◽  
Myeloid Cell ◽  
Expression Cloning ◽  
Immunoglobulin Gene ◽  
Cell Surface Molecule ◽  
Immune Effector ◽  
Surface Receptors ◽  
Molecular Features ◽  
Myeloid Cell Line ◽  
A Cell

IgA, the predominant isotype in secretions, mediates the neutralization and removal of environmental antigens from mucosal sites. Although cell surface receptors for the Fc region of IgA (Fc alpha R) have been implicated in a variety of immune effector mechanisms, the molecular features of Fc alpha R remain only marginally characterized. In this report, we describe the isolation of a clone from a myeloid cell line cDNA library that directs the expression of a cell surface molecule with IgA binding specificity. The cDNA encodes a peptide of Mr 30,000 including a putative transmembrane region with features atypical of conventional membrane-anchored proteins. Databank searches indicate that the human myeloid cell Fc alpha R sequence is unique, is a member of the immunoglobulin gene superfamily, and is related to Fc receptors for IgG (Fc gamma RI, II, and III) and IgE (Fc epsilon RI).

scholarly journals Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome

2020 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Martin N. Davis ◽  
Anna Barqué ◽  
Sylvie Ricard-Blum ◽  
Alexandra Naba
Keyword(s):  
Cell Surface ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Neural Crest Cell ◽  
Cell System ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Ecm Proteins ◽  
Terminal Fragment

ABSTRACTThe extracellular matrix (ECM) protein SNED1 has been shown to promote breast cancer metastasis and control neural crest cell-specific craniofacial development, but the cellular and molecular mechanisms by which it does so remain unknown. ECM proteins exert their functions by binding to cell surface receptors, sequestering growth factors, and interacting with other ECM proteins, actions that can be predicted using knowledge of protein’s sequence, structure and post-translational modifications. Here, we combined in-silico and in-vitro approaches to characterize the physico-chemical properties of SNED1 and infer its putative functions. To do so, we established a mammalian cell system to produce and purify SNED1 and its N-terminal fragment, which contains a NIDO domain. We have determined experimentally SNED1’s potential to be glycosylated, phosphorylated, and incorporated into insoluble ECM produced by cells. In addition, we used biophysical and computational methods to determine the secondary and tertiary structures of SNED1 and its N-terminal fragment. The tentative ab-initio model we built of SNED1 suggests that it is an elongated protein presumably able to bind multiple partners. Using computational predictions, we identified 114 proteins as putative SNED1 interactors. Pathway analysis of the newly-predicted SNED1 interactome further revealed that binding partners of SNED1 contribute to signaling through cell surface receptors, such as integrins, and participate in the regulation of ECM organization and developmental processes. Altogether, we provide a wealth of information on an understudied yet important ECM protein with the potential to decipher its functions in physiology and diseases.

Cell-surface receptors in health and disease.

1979 ◽  
Vol 25 (1) ◽  
pp. 11-19 ◽  
Author(s):  
M Blecher
Keyword(s):  
Cell Surface ◽  
Molecular Mechanisms ◽  
Diagnostic Procedures ◽  
Cell Surface Receptors ◽  
Pharmacological Agents ◽  
Surface Receptors ◽  
Health And Disease ◽  
Drugs In Blood

Abstract Assessment of interaction of hormones and neurotransmitters with their cell-surface receptors can lead to an understanding of the molecular mechanisms that underlie diseases in man involving resistance and supersensitivity to these humoral agents and to pharmacological agents. They can also lead to the development of simple diagnostic procedures for such disorders, as well as the development of radioreceptor assays for humoral agents and drugs in blood and tissues, assays which combine sensitivity comparable to those involving radiommunoassay with a greater biological accuracy.

scholarly journals Glycan-mediated enhancement of reovirus receptor binding

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Melanie Koehler ◽  
Pavithra Aravamudhan ◽  
Camila Guzman-Cardozo ◽  
Andra C. Dumitru ◽  
Jinsung Yang ◽  
...  
Keyword(s):  
Cell Surface ◽  
Molecular Mechanisms ◽  
Cell Surface Receptors ◽  
Viral Attachment ◽  
Surface Receptors ◽  
Force Microscopy ◽  
Atomic Force ◽  
Cell Components ◽  
A Cell ◽  
Attachment Proteins

Abstract Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multistep reovirus entry process are poorly understood. Using atomic force microscopy, we investigated how the reovirus σ1 attachment protein binds to both α-linked sialic acid (α-SA) and JAM-A cell-surface receptors. We discovered that initial σ1 binding to α-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following α-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of α-SA. Since ISVPs have an extended σ1 conformer, this finding suggests that α-SA binding triggers a conformational change in σ1. These results provide new insights into the function of viral attachment proteins in the initiation of infection and open new avenues for the use of reoviruses as oncolytic agents.

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.

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