TEM8 expression stimulates endothelial cell adhesion and migration by regulating cell?matrix interactions on collagen

Hotchkiss, Kylie A.; Basile, Cheryl M.; Spring, Simone C.; Bonuccelli, Gloria; Lisanti, Michael P.; Terman, Bruce I.

doi:10.1016/j.yexcr.2004.12.025

Cited by 105 publications

(111 citation statements)

References 25 publications

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“…Even though the lack of any known interaction motifs in the cytosolic domain prevents us from speculating about the mechanism for linkage to actin, the productive association of TEM8 with the cytoskeleton is predicted to confer stress resistance and mechanical coupling of the extracellular matrix ligand with the microfilament network. This function provides a mechanistic framework for the previous observation showing increased endothelial cell migration upon TEM8 expression (12). In addition to cell motility, linkage with the cytoskeleton has functional implications for morphogenesis, homeostasis and signal transduction, all processes relevant to angiogenesis (reviewed in Refs.…”

Section: Discussionmentioning

confidence: 81%

“…Antibody-based evidence suggests that TEM8 is also expressed in tissues where the bacterium spores enter the organism, such as skin, lungs, and small intestine (11). The soluble extracellular domain of TEM8 binds to collagen type 1 and gelatin (12) and co-immunoprecipitates with the C5 domain of collagen ␣3 (VI) (13). This evidence suggests interaction with molecules of the extracellular matrix (ECM); however the implications of these interactions for cell adhesion remain undetermined.…”

mentioning

confidence: 99%

“…This evidence suggests interaction with molecules of the extracellular matrix (ECM); however the implications of these interactions for cell adhesion remain undetermined. TEM8 also increases endothelial cell chemotactic activity on collagen substrata; however the mechanism for this function remains unclear (12). The second receptor, CMG2, is robustly induced during capillary tube formation in collagen gels and has a more ubiquitous pattern of expression than TEM8 (14).…”

mentioning

confidence: 99%

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Anthrax Toxin Receptor 1/Tumor Endothelium Marker 8 Mediates Cell Spreading by Coupling Extracellular Ligands to the Actin Cytoskeleton

Werner

Kowalczyk

Faúndez

2006

Journal of Biological Chemistry

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Tumor endothelial marker 8 (TEM8) is induced in tumorassociated vasculature and acts as a receptor for Protective Antigen (PA), the cell-binding component of the anthrax toxin determinant for toxin entrance into cells. However, the normal function for TEM8 remains unknown. We show that TEM8 functions as an adhesion molecule mediating cell spreading on immobilized PA and collagen I. The mechanism for TEM8 interaction with collagen I was cell type-specific, because binding to collagen I was abrogated by ␤1 integrin function blocking antibody in HEK293 cells, but not in primary synovial rabbit fibroblasts. Binding to PA remained unaffected by the addition of ␤1 integrin function blocking antibody. Whereas the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. Fusion of the cytosolic domain of TEM8 to the IL-2 receptor, conferred cell-spreading capability on IL-2 receptor antibody substrates. The cytoplasmic domain mediated linkage with the actin cytoskeleton as it co-precipitated actin and determined partitioning of TEM8 to the actin-containing detergent insoluble cellular fraction. TEM8 anchorage to actin was relevant as spreading was inhibited by the cytoskeleton-disrupting drug cytochalasin D, but persisted in the presence of the microtubule-depolymerizing drug nocodazole, and in cells lacking intermediate filaments. Thus, our results indicate that TEM8 is a new adhesion molecule linking collagen I or PA to the actin cytoskeleton.

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Section: Discussionmentioning

confidence: 81%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Anthrax Toxin Receptor 1/Tumor Endothelium Marker 8 Mediates Cell Spreading by Coupling Extracellular Ligands to the Actin Cytoskeleton

Werner

Kowalczyk

Faúndez

2006

Journal of Biological Chemistry

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“…Discovery of the first anthrax receptor ANTXR1 showed that the first 364 amino acids were identical to TEM8 [9]. Expression of the mouse homolog of ANTXR1 (TEM8) was found to be upregulated in the vasculature of the developing mouse embryo and also shown to be significantly upregulated in human tumor angiogenesis [10,11]. ANTXR1/TEM8 is expressed in a variety of tissues [12]; however, the precise physiological function of ANTXR1/TEM8 is not known.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore

Hesek

Zeng

2007

Microbial Pathogenesis

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We used quantitative real-time RT-PCR to not only investigate the mRNA levels of anthrax toxin receptor 1 (ANTXR1) and 2 (ANTXR2) in the murine J774A.1 macrophage cells and different tissues of mice, but also evaluate the effect of anthrax edema toxin and Bacillus anthracis Sterne spores on the expression of mRNA of these receptors. The mRNA transcripts of both receptors was detected in J774A.1 cells and mouse tissues such as the lung, heart, kidney, spleen, stomach, jejunum, brain, skeleton muscle, and skin. The ANTXR2 mRNA level was significantly higher than that of ANTXR1 in J774A.1 cells and all tissues examined. The mRNA expression of both receptors in the lung was the highest among the tissues evaluated. Interestingly, the mRNA expression of both receptors in J774A.1 cells was up-regulated by edema toxin. In addition, ANTXR mRNA expression in the lung was down-regulated after subcutaneous inoculation of B. anthracis Sterne spores as well as after intranasal administration of anthrax toxin-based vaccine BioThrax™. These results suggest that anthrax edema toxin and B. anthracis Sterne spore are involved in the ANTXR mRNA regulation in host cells.

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“…PA can also bind to β1 integrins, which potentiate the uptake of PA by macrophages [159]. The physiological role of TEM8 in mammals has been implicated in binding the extracellular matrix, directing endothelial migration and adhesion [160,161]. Less is known about CMG2 but evidence suggests a role in endothelial proliferation [162].…”

Section: Components Of the Exotoxin And Mechanism Of Internalizationmentioning

confidence: 99%

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

Lowe

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Bacillus anthracis is a Gram positive sporulating bacterium that is the causative agent of anthrax. Early steps in dissemination are understudied due to the asymptomatic and asynchronous nature of B. anthracis infections. The goals of these studies are to establish a model of the early steps of B. anthracis infections and examine how the initial site of infection and exotoxin production affect bacterial dissemination. In these studies, a mouse model was used in combination with a bioluminescent signature tagged library to determine how B.anthracis disseminates through the host and the roles of an exotoxin component, lethal factor, in colonization and dissemination. This library allowed for real time observation of dissemination and analysis of bacterial population dynamics. In the first set of experiments, mice were infected via inhalational or subcutaneous routes with the tagged library to determine how the bacterial population changed during dissemination. In inhalational and subcutaneous infections, the disseminated population was comprised of a small subset of the original library.This indicated the presence of a population bottleneck, a random decrease in genetic diversity during the infection. Surprisingly, the diminishment and location of the bottleneck varied depending on the initial site of infection. This suggested B. anthracis exploits multiple host environments and some sites may be more permissive for dissemination than others. In the second set of experiments, mice were infected with a signature tagged library where a portion of clones lacked lethal factor. Lethal factor is known to be an important virulence factor as deletion results in attenuated or complete loss of virulence in most animal models. Host survival increased when < 10% of the library produced lethal factor, but few other differences were observed. Furthermore, decreases in the proportion of lethal factor producing clones led to fewer clones disseminating. These findings suggest that a threshold of lethal factor must be ii produced for colonization and dissemination to occur in vivo. In total, this work provides an understanding of how B. anthracis is able to rapidly disseminate from a several tissues and gives insights in where future therapeutics should be focused to reduce disease incidence.iii

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TEM8 expression stimulates endothelial cell adhesion and migration by regulating cell?matrix interactions on collagen

Cited by 105 publications

References 25 publications

Anthrax Toxin Receptor 1/Tumor Endothelium Marker 8 Mediates Cell Spreading by Coupling Extracellular Ligands to the Actin Cytoskeleton

Anthrax Toxin Receptor 1/Tumor Endothelium Marker 8 Mediates Cell Spreading by Coupling Extracellular Ligands to the Actin Cytoskeleton

Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

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