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The IgCAMs CAR, BT-IgSF, and CLMP: Structure, Function, and Diseases

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Cell Adhesion Molecules

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 8))

Abstract

The coxsackie-adenovirus receptor (CAR) is the prototype of a small subfamily of IgCAMs composed of CAR itself, CLMP, BT-IgSF, ESAM, CTX, and A33. These six proteins are composed of one V-set and one C2-set Ig domains and a single transmembrane helix followed by a cytoplasmic stretch. They are localized in several tissues and organs and - except for ESAM, CTX, and A33 - are expressed in the developing brain. CAR becomes downregulated at early postnatal stages and is absent from the adult brain. CAR, CLMP, and BT-IgSF mediate homotypic aggregation. Interestingly, cell adhesion experiments, binding studies, and crystallographic investigations on the extracellular domain reveal a flexible ectodomain for CAR that mediates homophilic and heterophilic binding.

CAR has been extensively investigated in the context of gene therapy and diseases, while research on BT-IgSF and CLMP is at an early stage. Several mouse models as well as studies on patient tissues revealed an essential role for CAR in (1) the development of cardiac, renal, lymphatic, and intestinal tissue; (2) muscle pathology, remodeling, and regeneration; (3) tumor genesis/suppression and metastatic progression; and (4) in virus-mediated infections and gene therapy. Although the in vivo function of CAR in the brain has not been solved its developmentally regulated expression pattern in the brain as well as its function as CAM suggests that CAR might be implicated in neuronal network formation.

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Acknowledgments

The critical reading of the manuscript by Dr Alistair Garratt is greatly acknowledged. HL is recipient of stipend of the international PhD program of the HGF. The authors’ work was supported by a grant from DFG (Ra424/5-1).

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092, Berlin, Germany

    Jadwiga Schreiber, Hanna Langhorst, René Jüttner & Fritz G. Rathjen

  2. Department of Neuroscience, Erasmus University Medical Center, 2040, 3000 CA, Rotterdam, The Netherlands

    Jadwiga Schreiber

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  1. Jadwiga Schreiber
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Correspondence to Fritz G. Rathjen .

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  1. Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark

    Vladimir Berezin

  2. Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark

    Peter S. Walmod

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Schreiber, J., Langhorst, H., Jüttner, R., Rathjen, F.G. (2014). The IgCAMs CAR, BT-IgSF, and CLMP: Structure, Function, and Diseases. In: Berezin, V., Walmod, P. (eds) Cell Adhesion Molecules. Advances in Neurobiology, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8090-7_2

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