Expression and distribution of the receptors for coxsackievirus B3 during fetal development of the Balb/c mouse and of their brain cells in culture

Xu, Ruliang; Crowell, Richard L.

doi:10.1016/s0168-1702(96)01398-6

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…In agreement with previous studies (Xu and Crowell, 1996;Honda et al, 2000), we detected CAR on all neural cells in sections of the retina. However, CAR was enriched at specific sites, including a strong localization on RGC axons facing the vitreous body, suggesting that CAR might mediate an interaction of RGC axons with ECM proteins of the inner limiting membrane, or with other RGC axons.…”

Section: Car Localization In the Developing Retina Is Dynamically Regsupporting

confidence: 93%

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The Coxsackievirus–Adenovirus Receptor Reveals Complex Homophilic and Heterophilic Interactions on Neural Cells

Patzke¹,

Max²,

Behlke³

et al. 2010

J. Neurosci.

119

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The coxsackievirus-adenovirus receptor (CAR) is a member of the Ig superfamily strongly expressed in the developing nervous system. Our histological investigations during development reveal an initial uniform distribution of CAR on all neural cells with a concentration on membranes that face the margins of the nervous system (e.g., the basal laminae and the ventricular side). At more advanced stages, CAR becomes downregulated and restricted to specific regions including areas rich in axonal and dendritic surfaces.To study the function of CAR on neural cells, we used the fiber knob of the adenovirus, extracellular CAR domains, blocking antibodies to CAR, as well as CAR-deficient neural cells. Blocking antibodies were found to inhibit neurite extension in retina organ and retinal explant cultures, whereas the application of the recombinant fiber knob of the adenovirus subtype Ad2 or extracellular CAR domains promoted neurite extension and adhesion to extracellular matrices.We observed a promiscuous interaction of CAR with extracellular matrix glycoproteins, which was deduced from analytical ultracentrifugation experiments, affinity chromatography, and adhesion assays. The membrane proximal Ig domain of CAR, termed D2, was found to bind to a fibronectin fragment, including the heparin-binding domain 2, which promotes neurite extension of wild type, but not of CAR-deficient neural cells. In contrast to heterophilic interactions, homophilic association of CAR involves both Ig domains, as was revealed by ultracentrifugation, chemical cross-linking, and adhesion studies. The results of these functional and binding studies are correlated to a U-shaped homodimer of the complete extracellular domains of CAR detected by x-ray crystallography.

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Section: Car Localization In the Developing Retina Is Dynamically Regsupporting

confidence: 93%

“…In the adult heart, CAR is predominantly localized at the intercalated discs (Shaw et al, 2004). In the vertebrate nervous system, CAR is strongly expressed during embryogenesis, followed by drastic reduction at early postnatal stages (Xu and Crowell, 1996;Honda et al, 2000;Dorner et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Coxsackievirus–Adenovirus Receptor Reveals Complex Homophilic and Heterophilic Interactions on Neural Cells

Patzke¹,

Max²,

Behlke³

et al. 2010

J. Neurosci.

119

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show abstract

“…3,4 How this role is subverted during malignant progression is unknown, but to associate CAR with the 'differentiated state' (because it is an epithelial adhesion molecule in polarized epithelia) is likely incomplete, or incorrect. To suggest that CAR functions solely as a mediator of barrier function in polarized epithelia also does not appear to be consistent with its emerging portrait as a developmentally expressed adhesion molecule in the mammalian brain, [69][70][71] heart, 8,72,73 and skeletal muscle, 74 nor with its characterization as a mediator of heterotypic cell interactions. 10,68 The fact that CAR is ubiquitously expressed in both epithelium-and mesenchyme-derived tissues (apparently including hematopoietic precursors 53 ) during development suggests a more generalized role for CAR.…”

Section: Discussionmentioning

confidence: 95%

CAR mediates efficient tumor engraftment of mesenchymal type lung cancer cells

Veena

Qin

Andersson

et al. 2009

Laboratory Investigation

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The coxsackie-adenovirus receptor (CAR) is a developmentally regulated intercellular adhesion molecule that was previously observed to be required for efficient tumor formation. To confirm that observation, we compared the tumorigenicity of clonally derived test and control cell subsets that were genetically modified for CAR. Silencing CAR in lung cancer cells with high constitutive expression reduced engraftment efficiency. Conversely, overexpressing CAR in lung cancer cells with low constitutive expression did not affect tumor formation or growth kinetics. A blocking antibody to the extracellular domain of CAR inhibited tumor engraftment, implicating that domain as being important to this process. However, differences in adhesion properties attributable to this domain (barrier function and aggregation) could not be distinguished in the test groups in vitro, and the mechanisms underlying CAR's contribution to tumor engraftment remain elusive. Because high CAR cells displayed a spindle-shaped morphology at baseline, we considered whether this expression was an accompaniment of other mesenchymal features in these lung cancer cells. Molecular correlates of CAR were compared in model epithelial and mesenchymal type lung cancer cells. CAR expression is associated with an absence of E-cadherin, diminished expression of a-and g-catenin, and increased Zeb1, Snail, and vimentin expression in lung cancer cells. In contrast, epithelial type (NCI-H292, Calu3) lung cancer cells show comparatively low CAR expression. These data suggest that if the mesenchymal cell phenotype is an accurate measure of an undifferentiated and invasive state, then CAR expression may be more closely aligned with this phenotype of lung cancer cells.

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“…In an effort to develop an alternative model for the study of VZV infection, newborn rats were tested as they have been reported to be far more susceptible than adult rats to infection with HSV [Tanaka and Southam, 1965] or coxsackie viruses [Xu and Cromwell, 1996]. In addition, human infants born to mothers who experience varicella during pregnancy [Brunell and Kotchmar, 1981] or infants who get varicella during the first month of life [Baba et al, 1986] often develop zoster in early life, suggesting that latency may be more readily established in newborns.…”

Section: Introductionmentioning

confidence: 99%

Viral gene expression in rat trigeminal ganglia following neonatal infection with varicella-zoster virus

et al. 1999

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Newborn rats were injected intraperitoneally with uninfected human cells or cell infected with 56,000 pfu of varicella-zoster virus (VZV). Five to 6 weeks later, trigeminal ganglia were harvested and tested for VZV DNA and RNA by PCR. VZV gene 21 and 40 DNA were detected in most infected animals. Gene 21 RNA also was detected in ganglia from most infected animals, but not gene 40 RNA, paralleling previous observations in latently infected human ganglia. The neonatal rat may represent a useful new model for the study of VZV latency.

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Expression and distribution of the receptors for coxsackievirus B3 during fetal development of the Balb/c mouse and of their brain cells in culture

Cited by 25 publications

References 29 publications

The Coxsackievirus–Adenovirus Receptor Reveals Complex Homophilic and Heterophilic Interactions on Neural Cells

The Coxsackievirus–Adenovirus Receptor Reveals Complex Homophilic and Heterophilic Interactions on Neural Cells

CAR mediates efficient tumor engraftment of mesenchymal type lung cancer cells

Viral gene expression in rat trigeminal ganglia following neonatal infection with varicella-zoster virus

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