Coxsackievirus and adenovirus receptor is essential for cardiomyocyte development

Asher, Damon R.; Cerny, Anna M.; Weiler, Sarah R.; Horner, James W.; Keeler, Marilyn L.; Neptune, Mychell A.; Jones, Stephen N.; Bronson, Roderick T.; DePinho, Ronald A.; Finberg, Robert W.

doi:10.1002/gene.20127

Cited by 85 publications

(74 citation statements)

References 38 publications

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“…CAR is strongly expressed in multiple tissues during the embryonic and neonatal phase of rats and mice, but its level attenuated substantially in brains, hearts and became undetectable in muscles of adult animals [3,4,7]. The high abundance of CAR during embryonic and neonatal periods has been ascribed to its role in mediating cell adhesion during tissue morphogenesis [4,6,7].…”

Section: Discussionmentioning

confidence: 99%

“…The high abundance of CAR during embryonic and neonatal periods has been ascribed to its role in mediating cell adhesion during tissue morphogenesis [4,6,7]. In adult rat testes, extensive restructuring of cytoarchitecture occurs continuously at different stages of seminiferous epithelial cycle [13], which enables the translocation of developing germ cells from the basal to the adluminal compartment.…”

Section: Discussionmentioning

confidence: 99%

“…The availability of CAR on cell surface is a determining factor of a cell's susceptibility to adenoviral vectors for gene delivery [2]. Therefore, extensive studies have been carried out to establish the expression profile of CAR in a variety of human tissues that are of interest to gene therapy, such as brain, heart and muscles [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Coxsackie and adenovirus receptor (CAR) is a product of Sertoli and germ cells in rat testes which is localized at the Sertoli–Sertoli and Sertoli–germ cell interface

Wang

Mruk

Lee

et al. 2007

Experimental Cell Research

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The coxsackie and adenovirus receptor (CAR), a putative cell-cell adhesion molecule, has attracted wide interest due to its importance in viral pathogenesis and in mediating adenoviral gene delivery. However, the distribution pattern and physiological function of CAR in the testis is still not clear. Here, we identified CAR in Sertoli cells and germ cells of rats. In vivo studies have shown that CAR resides at the blood-testis barrier as well as at the ectoplasmic specialization. The persistent expression of CAR in rat testes from neonatal period throughout adulthood implicates its role in spermatogenesis. Using primary Sertoli cell cultures, we observed a significant induction of CAR during the formation of Sertoli cell epithelium. Furthermore, CAR was seen to be concentrated at inter-Sertoli cell junctions, colocalizing with tight junction protein marker ZO-1 and adherens junction protein N-cadherin. CAR was also found to be associated with proteins of Src kinase family and its protein level declined after TNFα treatment in Sertoli cell cultures. Immunofluorescent staining of isolated germ cells has revealed the presence of CAR on spermatogonia, spermatocytes, round spermatids and elongate spermatids. Taken together, we propose that CAR functions as an adhesion molecule in maintaining the inter-Sertoli cell junctions at the basal compartment of the seminiferous epithelium. In addition, CAR may confer adhesion between Sertoli and germ cells at the Sertoli-germ cell interface. It is possible that the receptor utilized by viral pathogens to breakthrough the epithelial barrier was also employed by developing germ cells to migrate through the inter-Sertoli cell junctions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Coxsackie and adenovirus receptor (CAR) is a product of Sertoli and germ cells in rat testes which is localized at the Sertoli–Sertoli and Sertoli–germ cell interface

Wang

Mruk

Lee

et al. 2007

Experimental Cell Research

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“…The absence of CAR in mice results in lethality at embryonic day 11 because of malformations of the heart (Asher et al, 2005;Dorner et al, 2005;Chen et al, 2006). In the adult heart, ablation of CAR results in disturbed conduction of electrical activity from the atrium (A) to the ventricle (V) as indicated by a prolonged PR interval in electrocardiogram plots.…”

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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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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“…[4][5][6] CAR has many physiological functions, such as formation of a tight junction in epithelial cells, [7][8][9] growth-inhibitory activity in tumor cells, 10,11 and early embryonic cardiac development. 12,13 One of the characteristics of members of the Ig superfamily is sequence homology among the members. 14 For example, CAR is structurally similar to CAR-like membrane protein (CLMP), 15 brain-and testis-specific Ig superfamily (BT-IgSF), 16 and endothelial cell-selective adhesion molecule (ESAM).…”

Section: Introductionmentioning

confidence: 99%

Positive and negative regulation of adenovirus infection by CAR-like soluble protein, CLSP

et al. 2007

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Coxsackievirus and adenovirus receptor is essential for cardiomyocyte development

Cited by 85 publications

References 38 publications

Coxsackie and adenovirus receptor (CAR) is a product of Sertoli and germ cells in rat testes which is localized at the Sertoli–Sertoli and Sertoli–germ cell interface

Coxsackie and adenovirus receptor (CAR) is a product of Sertoli and germ cells in rat testes which is localized at the Sertoli–Sertoli and Sertoli–germ cell interface

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

Positive and negative regulation of adenovirus infection by CAR-like soluble protein, CLSP

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