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

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

doi:10.1007/978-1-4614-8090-7_2

Cited by 14 publications

(9 citation statements)

References 141 publications

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“…Moreover, the domain architectures of both proteins resemble that of several types of receptors and cell-adhesion molecules known to act as self-ligands by binding to themselves across opposing cell membranes (homophilic trans interactions) [30, 31]. We therefore hypothesized that Alr1 and Alr2 might function via homophilic trans interactions and, further, that the protein isoforms encoded by different alleles would only bind to very similar or identical partners, providing a molecular mechanism for self-discrimination.…”

Section: Resultsmentioning

confidence: 99%

Allorecognition Proteins in an Invertebrate Exhibit Homophilic Interactions

2015

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Summary Sessile colonial invertebrates—animals such as sponges, corals, bryozoans, and ascidians—can distinguish between their own tissues and those of conspecifics upon contact [1]. This ability, called allorecognition, mediates spatial competition and can prevent stem cell parasitism by ensuring that colonies only fuse with self or close kin. In every taxon studied to date, allorecognition is controlled by one or more highly polymorphic genes [2–8]. However, in no case is it understood how the proteins encoded by these genes discriminate self from non-self. In the cnidarian Hydractinia symbiolongicarpus, allorecognition is controlled by at least two highly polymorphic allorecognition genes, Alr1 and Alr2 [3, 5, 9–12]. Sequence variation at each gene predicts allorecognition in laboratory strains such that colonies reject if they do not share a common allele at either locus, fuse temporarily if they share an allele at only one locus, or fuse permanently if they share an allele at both genes [5, 9]. Here, we show that the gene products of Alr1 and Alr2 (Alr1 and Alr2) are self-ligands with extraordinary specificity. Using an in vitro cell aggregation assay, we found that Alr1 and Alr2 bind to themselves homophilically across opposing cell membranes. For both proteins, each isoform bound only to itself or to an isoform of nearly identical sequence. These results provide a mechanistic explanation for the exquisite specificity of Hydractinia allorecognition. Our results also indicate that hydroids have evolved a molecular strategy of self-recognition that is unique among characterized allorecognition systems within and outside invertebrates.

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Section: Resultsmentioning

confidence: 99%

Allorecognition Proteins in an Invertebrate Exhibit Homophilic Interactions

2015

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“…The CAR-related proteins form a subgroup within the larger subgroup of CTX (the cortical thymocyte marker in Xenopus) of Ig-like cell adhesion molecules (Chretien et al, 1998;Du Pasquier and Chrétien, 1996). Besides CAR, CLMP, BT-IgSF and ESAM (endothelial cell-selective adhesion molecule) are assigned to this CAR subgroup (Schreiber et al, 2014). These are type I transmembrane glycoproteins sharing an identical overall domain organization including two extracellular Ig domains, a transmembrane segment and a cytoplasmic tail.…”

Section: Structural Features Of Car-related Cell Adhesion Moleculesmentioning

confidence: 99%

Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell adhesion molecules in health and disease

Matthäus

Langhorst

Schütz

et al. 2017

Molecular and Cellular Neuroscience

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The immunoglobulin superfamily represents a diverse set of cell-cell contact proteins and includes well-studied members such as NCAM1, DSCAM, L1 or the contactins which are strongly expressed in the nervous system. In this review we put our focus on the biological function of a less understood subgroup of Ig-like proteins composed of CAR (coxsackievirus and adenovirus receptor), CLMP (CAR-like membrane protein) and BT-IgSF (brain and testis specific immunoglobulin superfamily). The CAR-related proteins are type I transmembrane proteins containing an N-terminal variable (V-type) and a membrane proximal constant (C2-type) Ig domain in their extracellular region which are implicated in homotypic adhesion. They are highly expressed during embryonic development in a variety of tissues including the nervous system whereby in adult stages the protein level of CAR and CLMP decreases, only BT-IgSF expression increases within age. CAR-related proteins are concentrated at specialized cell-cell communication sites such as gap or tight junctions and are present at the plasma membrane in larger protein complexes. Considerable progress has been made on the molecular structure and interactions of CAR while research on CLMP and BT-IgSF is at an early stage. Studies on mouse mutants revealed biological functions of CAR in the heart and for CLMP in the gastrointestinal and urogenital systems. Furthermore, CAR and BT-IgSF appear to regulate synaptic function in the hippocampus.

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“…This in our opinion at least allows two conclusions: 1. There seems to be a redundancy with regard to Super Ig cell adhesion molecules possessing only 2 extracellular IgG domains and other members expressed in podocytes could potentially take over CXADR’s function [24, 35]. 2.…”

Section: Discussionmentioning

confidence: 99%

Podocyte-Specific Deletion of Murine CXADR Does Not Impair Podocyte Development, Function or Stress Response

et al. 2015

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The coxsackie- and adenovirus receptor (CXADR) is a member of the immunoglobulin protein superfamily, present in various epithelial cells including glomerular epithelial cells. Beside its known function as a virus receptor, it also constitutes an integral part of cell-junctions. Previous studies in the zebrafish pronephros postulated a potential role of CXADR for the terminal differentiation of glomerular podocytes and correct patterning of the elaborated foot process architecture. However, due to early embryonic lethality of constitutive Cxadr knockout mice, mammalian data on kidney epithelial cells have been lacking. Interestingly, Cxadr is robustly expressed during podocyte development and in adulthood in response to glomerular injury. We therefore used a conditional transgenic approach to elucidate the function of Cxadr for podocyte development and stress response. Surprisingly, we could not discern a developmental phenotype in podocyte specific Cxadr knock-out mice. In addition, despite a significant up regulation of CXADR during toxic, genetic and immunologic podocyte injury, we could not detect any impact of Cxadr on these injury models. Thus these data indicate that in contrast to lower vertebrate models, mammalian podocytes have acquired molecular programs to compensate for the loss of Cxadr.

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

Cited by 14 publications

References 141 publications

Allorecognition Proteins in an Invertebrate Exhibit Homophilic Interactions

Allorecognition Proteins in an Invertebrate Exhibit Homophilic Interactions

Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell adhesion molecules in health and disease

Podocyte-Specific Deletion of Murine CXADR Does Not Impair Podocyte Development, Function or Stress Response

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