Junction Adhesion Molecule Is a Receptor for Reovirus
TL;DR: Reovirus interaction with cell-surface receptors is a critical determinant of both cell-type specific tropism and virus-induced intracellular signaling events that culminate in cell death.
About: This article is published in Cell.The article was published on 2001-02-09 and is currently open access. It has received 627 citations till now. The article focuses on the topics: Tropism & Junctional Adhesion Molecule A.
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TL;DR: A group of integral membrane proteins-occludin, claudins, and junction adhesion molecules-interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity.
Abstract: Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins-occludin, claudins, and junction adhesion molecules-interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity.
1,332 citations
Cites background from "Junction Adhesion Molecule Is a Rec..."
...This interaction stimulates nuclear factor- B (NF- B) activation, which results in cellular apoptosis (16)....
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TL;DR: Using an iterative expression cloning approach, claudin-1 (CLDN1), a tight junction component that is highly expressed in the liver, is identified as essential for HCV entry and a new target for antiviral drug development.
Abstract: Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. A better understanding of the viral life cycle, including the mechanisms of entry into host cells, is needed to identify novel therapeutic targets. Although HCV entry requires the CD81 co-receptor, and other host molecules have been implicated, at least one factor critical to this process remains unknown (reviewed in refs 1-3). Using an iterative expression cloning approach we identified claudin-1 (CLDN1), a tight junction component that is highly expressed in the liver, as essential for HCV entry. CLDN1 is required for HCV infection of human hepatoma cell lines and is the first factor to confer susceptibility to HCV when ectopically expressed in non-hepatic cells. Discrete residues within the first extracellular loop (EL1) of CLDN1, but not protein interaction motifs in intracellular domains, are critical for HCV entry. Moreover, antibodies directed against an epitope inserted in the CLDN1 EL1 block HCV infection. The kinetics of this inhibition indicate that CLDN1 acts late in the entry process, after virus binding and interaction with the HCV co-receptor CD81. With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development.
1,259 citations
TL;DR: How the molecular architectures and interactions may represent a mechanistic basis for the function and regulation of junctions, focusing on junction assembly and permeability regulation, is emphasized.
Abstract: Intercellular junctions mediate adhesion and communication between adjoining endothelial and epithelial cells. In the endothelium, junctional complexes comprise tight junctions, adherens junctions, and gap junctions. The expression and organization of these complexes depend on the type of vessels and the permeability requirements of perfused organs. Gap junctions are communication structures, which allow the passage of small molecular weight solutes between neighboring cells. Tight junctions serve the major functional purpose of providing a "barrier" and a "fence" within the membrane, by regulating paracellular permeability and maintaining cell polarity. Adherens junctions play an important role in contact inhibition of endothelial cell growth, paracellular permeability to circulating leukocytes and solutes. In addition, they are required for a correct organization of new vessels in angiogenesis. Extensive research in the past decade has identified several molecular components of the tight and adherens junctions, including integral membrane and intracellular proteins. These proteins interact both among themselves and with other molecules. Here, we review the individual molecules of junctions and their complex network of interactions. We also emphasize how the molecular architectures and interactions may represent a mechanistic basis for the function and regulation of junctions, focusing on junction assembly and permeability regulation. Finally, we analyze in vivo studies and highlight information that specifically relates to the role of junctions in vascular endothelial cells.
1,185 citations
Cites background from "Junction Adhesion Molecule Is a Rec..."
...Interestingly, JAM-A may also mediate heterophilic adhesion to ligands as diverse as the leukocyte L 2-integrin (249) and the attachment protein sigma1 of Reovirus (28)....
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TL;DR: Advances in the knowledge of the molecular structure of TJ support previous physiological models that exhibited TJ as dynamic structures that present distinct permeability and morphological characteristics in different tissues and in response to changing natural, pathological or experimental conditions.
Abstract: A fundamental function of epithelia and endothelia is to separate different compartments within the organism and to regulate the exchange of substances between them. The tight junction (TJ) constitutes the barrier both to the passage of ions and molecules through the paracellular pathway and to the movement of proteins and lipids between the apical and the basolateral domains of the plasma membrane. In recent years more than 40 different proteins have been discovered to be located at the TJs of epithelia, endothelia and myelinated cells. This unprecedented expansion of information has changed our view of TJs from merely a paracellular barrier to a complex structure involved in signaling cascades that control cell growth and differentiation. Both cortical and transmembrane proteins integrate TJs. Among the former are scaffolding proteins containing PDZ domains, tumor suppressors, transcription factors and proteins involved in vesicle transport. To date two components of the TJ filaments have been identified: occludin and claudin. The latter is a protein family with more than 20 members. Both occludin and claudins are integral proteins capable of interacting adhesively with complementary molecules on adjacent cells and of co-polymerizing laterally. These advancements in the knowledge of the molecular structure of TJ support previous physiological models that exhibited TJ as dynamic structures that present distinct permeability and morphological characteristics in different tissues and in response to changing natural, pathological or experimental conditions.
1,096 citations
TL;DR: These findings for the first time clearly separate the proapoptotic effects of IFN-γ and TNF-α from their abilities to disrupt barrier function.
Abstract: It is well known that inflammatory conditions of the intestinal mucosa result in compromised barrier function. Inflammation is characterized by an influx into the mucosa of immune cells that influence epithelial function by releasing proinflammatory cytokines such as IFN-γ and TNF-α. Mucosal barrier function is regulated by the epithelial apical junctional complex (AJC) consisting of the tight junction and the adherens junction. Since the AJC regulates barrier function, we analyzed the influence of IFN-γ and TNF-α on its structure/function and determined the contribution of apoptosis to this process using a model intestinal epithelial cell line, T84, and IFN-γ and TNF-α. AJC structure/function was analyzed by confocal microscopy, biochemical analysis, and physiologic measurement of epithelial gate/fence function. Apoptosis was monitored by determining cytokeratin 18 cleavage and caspase-3 activation. IFN-γ induced time-dependent disruptions in epithelial gate function that were potentiated by coincubation with TNF-α. Tight junction fence function was somewhat disrupted. Cytokine treatment was associated with internalization of AJC transmembrane proteins, junction adhesion molecule 1, occludin, and claudin-1/4 with minimal effects on the cytoplasmic plaque protein zonula occludens 1. Detergent solubility profiles of junction adhesion molecule 1 and E-cadherin and their affiliation with “raft-like” membrane microdomains were modified by these cytokines. Inhibition of cytokine-induced apoptosis did not block induced permeability defects; further emphasizing their primary influence on the epithelial AJC structure and barrier function. Our findings for the first time clearly separate the proapoptotic effects of IFN-γ and TNF-α from their abilities to disrupt barrier function.
847 citations
Cites background from "Junction Adhesion Molecule Is a Rec..."
...The functional significance of altered JAM-1 expression in membrane rafts may relate to its status as a putative target for pathogens such as reovirus (62)....
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References
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4,925 citations
"Junction Adhesion Molecule Is a Rec..." refers methods in this paper
...(Hirt, 1967), amplified in bacteria, and used in three subsequent rounds of FACS enrichment....
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TL;DR: It is argued that NF-κB functions more generally as a central regulator of stress responses and pairing stress responsiveness and anti-apoptotic pathways through the use of a common transcription factor may result in increased cell survival following stress insults.
Abstract: Sixteen years have passed since the description of the nuclear factor-кB (NF-кB) as a regulator of к light-chain gene expression in murine B lymphocytes (Sen & Baltimore, 1986a) During that time, over 4,000 publications have appeared, characterizing the family of Rel/NF-кB transcription factors involved in the control of a large number of normal and pathological cellular processes The physiological functions of NF-кB proteins include immunological and inflammatory responses, developmental processes, cellular growth and modulating effects on apoptosis In addition, these factors are activated in a number of diseases, including cancer, arthritis, acute and chronic inflammatory states, asthma, as well as neurodegenerative and heart diseases
3,728 citations
"Junction Adhesion Molecule Is a Rec..." refers methods in this paper
...Cells were incubated at 378C for various intervals,flammatory cytokines involved in the activation and atand viral titers in lysates were determined by plaque assay.traction of immune effector cells (Pahl, 1999)....
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TL;DR: Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.
Abstract: A complementary DNA clone has been isolated that encodes a coxsackievirus and adenovirus receptor (CAR). When transfected with CAR complementary DNA, nonpermissive hamster cells became susceptible to coxsackie B virus attachment and infection. Furthermore, consistent with previous studies demonstrating that adenovirus infection depends on attachment of a viral fiber to the target cell, CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and showed a 100-fold increase in susceptibility to virus-mediated gene transfer. Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.
3,128 citations
"Junction Adhesion Molecule Is a Rec..." refers methods in this paper
...PCR product and Fc-hCAR-pCDNA vided into sub-pools of 5 colonies, and plasmid from sub-pools was 3.1 (Bergelson et al., 1997) were subjected to restriction digest with tested for the capacity to confer enhanced FITC-T3SA2 binding to HindIII and BamHI, resulting in excision of hCAR-encoding…...
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...(Fc-hCAR) was used as a control for nonspecific interactions (Bergelson et al., 1997)....
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TL;DR: Immunological synapse formation is now shown to be an active and dynamic mechanism that allows T cells to distinguish potential antigenic ligands and was a determinative event for T cell proliferation.
Abstract: The specialized junction between a T lymphocyte and an antigen-presenting cell, the immunological synapse, consists of a central cluster of T cell receptors surrounded by a ring of adhesion molecules. Immunological synapse formation is now shown to be an active and dynamic mechanism that allows T cells to distinguish potential antigenic ligands. Initially, T cell receptor ligands were engaged in an outermost ring of the nascent synapse. Transport of these complexes into the central cluster was dependent on T cell receptor—ligand interaction kinetics. Finally, formation of a stable central cluster at the heart of the synapse was a determinative event for T cell proliferation. A critical event in the initiation of the adaptive
2,988 citations
"Junction Adhesion Molecule Is a Rec..." refers background in this paper
...This interval wouldgaged by both antigen and accessory molecules to initiallow for multiple rounds of viral replication prior to cellate effector functions (Grakoui et al., 1999)....
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TL;DR: A role for NF-κB in growth factor signalling is established and an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-κBs pathway is defined, thus linking anti-APoptotic signalling with transcription machinery.
Abstract: The mechanisms of cell proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided1,2. Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation1, but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-κB3,4,5 is important in PDGF signalling. NF-κB transmits two signals: one is required for the induction of proto-oncogene c-myc and proliferation, and the second, an anti-apoptotic signal, counterbalances c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF activates NF-κB through Ras and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the IκB kinase (IKK); NF-κB thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway6,7. We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-κB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-κB pathway, thus linking anti-apoptotic signalling with transcription machinery.
1,819 citations
"Junction Adhesion Molecule Is a Rec..." refers background in this paper
...Although T3SA1 is Baldwin, 1999; Romashkova and Makarov, 1999)....
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