Catabolism of the human erythrocyte C3b/C4b receptor (CR1, CD35) : vesiculation and/or proteolysis?

Dervillez, Xavier; Oudin, S.; Libyh, M. Tonye; Tabary, Thierry; Réveil, Brigitte; Philbert, F.; Bougy, F.; Pluot, M; Cohen, Jacques H. M.

doi:10.1016/s0162-3109(97)00066-0

Cited by 19 publications

(15 citation statements)

References 45 publications

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“…The mechanism responsible for low CR1 on thalassemic RBCs is unclear. CR1 is preferentially lost in vesicles from the cell surface as RBCs age or become ATP-depleted (43,44). It is possible that biochemical abnormalities in thalassemic RBCs promote a similar process that would reduce their CR1 level.…”

Section: Discussionmentioning

confidence: 99%

A human complement receptor 1 polymorphism that reducesPlasmodium falciparumrosetting confers protection against severe malaria

Cockburn

Mackinnon

O’Donnell

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

217

186

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Parasitized red blood cells (RBCs) from children suffering from severe malaria often adhere to complement receptor 1 (CR1) on uninfected RBCs to form clumps of cells known as ''rosettes.'' Despite a well documented association between rosetting and severe malaria, it is controversial whether rosetting is a cause or a correlate of parasite virulence. CR1-deficient RBC show greatly reduced rosetting; therefore, we hypothesized that, if rosetting is a direct cause of malaria pathology, CR1-deficient individuals should be protected against severe disease. In this study, we show that RBC CR1 deficiency occurs in up to 80% of healthy individuals from the malaria-endemic regions of Papua New Guinea. This RBC CR1 deficiency is associated with polymorphisms in the CR1 gene and, unexpectedly, with ␣-thalassemia, a common genetic disorder in Melanesian populations. Analysis of a case-control study demonstrated that the CR1 polymorphisms and ␣-thalassemia independently confer protection against severe malaria. We have therefore identified CR1 as a new malaria resistance gene and provided compelling evidence that rosetting is an important parasite virulence phenotype that should be a target for drug and vaccine development.

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Section: Discussionmentioning

confidence: 99%

A human complement receptor 1 polymorphism that reducesPlasmodium falciparumrosetting confers protection against severe malaria

Cockburn

Mackinnon

O’Donnell

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

217

186

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“…Receptor-Ligand Binding Assay-Assay were modified according to a previously published protocol (37). Tissue culture 96-well plates were coated with different concentrations of type I collagen or bovine serum albumin overnight.…”

Section: Methodsmentioning

confidence: 99%

Mapping of Epitopes in Discoidin Domain Receptor 1 Critical for Collagen Binding

Curat¹,

Eck²,

Dervillez³

et al. 2001

Journal of Biological Chemistry

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The binding and activation of the discoidin domain receptor 1 by collagen has led to the conclusion that proteins from the extracellular matrix can directly induce receptor tyrosine kinase-mediated signaling cascades. A region in the extracellular domain of DDR1 homologous to the Dictyostelium discoideum protein discoidin-I is also present in the secreted human protein RS1. Mutations in RS1 cause retinoschisis, a genetic disorder characterized by ablation of the retina. By introducing point mutations into the discoidin domain of DDR1 at positions homologous to the retinoschisis mutations, ligand binding epitopes in the discoidin domain of DDR1 were mapped. Surprisingly, some residues only affected receptor phosphorylation, whereas others influenced both collagen-binding and receptor activation. Furthermore, two truncated DDR1 variants, lacking either the discoidin domain or the stalk region between the discoidin and transmembrane domain, were generated. We showed that (i) the discoidin domain was necessary and sufficient for collagen binding, (ii) only the region between discoidin and transmembrane domain was glycosylated, and (iii) the entire extracellular domain was essential for transmembrane signaling. Using these results, we were able to predict key sites in the collagen-binding epitope of DDR1 and to suggest a potential mechanism of signaling.Discoidin domain receptors 1 and 2 (DDR1 and DDR2) 1 have been recognized as a distinct tyrosine kinase receptor subfamily because of structural and functional homologies. In their extracellular region, both receptors show a domain homologous to the Dictyostelium discoideum protein discoidin I. DDR1 and DDR2 are also functionally related by the observation that collagen acts as cognate ligand for both receptors. Whereas DDR1 activation is achieved by all collagens so far tested (types I-VI and VIII), DDR2 is only activated by fibrillar collagens, in particular by collagen type I and type III. In contrast to most other tyrosine kinase receptors, activation of DDRs can take several hours (1, 2).The cDNA coding for human DDR1 has been cloned from several tissues or carcinoma cells (3-7). Gene orthologs to human DDR1 have been identified in mice, rats, and Caenorhabditis elegans (8 -10). Expression of human DDR1 is predominantly seen in epithelial cells, particularly from kidney, lung, gastrointestinal tract, and brain, but also in corneal and dermal fibroblasts (7, 9, 11-13). DDR1 seems to be also involved in the differentiation of cerebellar granular neurons (14). Upregulated DDR1 expression has been reported from breast, ovarian, esophagus and brain tumors (5,(15)(16)(17)(18)(19). Human DDR1 is located on chromosome 6p21.3 in close proximity to HLA genes, which belong to the telomeric region (class I) of the major histocompatibility complex (20). The juxtamembrane regions in DDR1 and DDR2 are much longer than in other receptor tyrosine kinases (176 and 147 amino acids, respectively). Furthermore, the extracellular domain of DDR1 is shed by an unidentified protease, res...

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“…Finally, CR1 is also present in circulation in a soluble form (sCR1) [26], resulting from either the proteolysis of the membrane-bound form of CR1 [27] or exocytosis from erythrocytes (E) [28]. It is hypothesized that sCR1 is a locally active molecule that seems to have highly efficacious complement regulatory and anti-inflammatory activities [16,29].…”

Section: Introductionmentioning

confidence: 99%

Inherited and Acquired Decrease in Complement Receptor 1 (CR1) Density on Red Blood Cells Associated with High Levels of Soluble CR1 in Alzheimer’s Disease

Mahmoudi

Feldman

Kisserli

et al. 2018

IJMS

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The complement receptor 1 (CR1) gene was shown to be involved in Alzheimer’s disease (AD). We previously showed that AD is associated with low density of the long CR1 isoform, CR1*2 (S). Here, we correlated phenotype data (CR1 density per erythrocyte (CR1/E), blood soluble CR1 (sCR1)) with genetic data (density/length polymorphisms) in AD patients and healthy controls. CR1/E was enumerated using flow cytometry, while sCR1 was quantified by ELISA. CR1 polymorphisms were assessed using restriction fragment length polymorphism (RFLP), pyrosequencing, and high-resolution melting PCR. In AD patients carrying the H allele (HindIII polymorphism) or the Q allele (Q981H polymorphism), CR1/E was significantly lower when compared with controls carrying the same alleles (p < 0.01), contrary to sCR1, which was significantly higher (p < 0.001). Using multivariate analysis, a reduction of 6.68 units in density was associated with an increase of 1% in methylation of CR1 (estimate −6.68; 95% confidence intervals (CIs) −12.37, −0.99; p = 0.02). Our data show that, in addition to inherited genetic factors, low density of CR1/E is also acquired. The involvement of CR1 in the pathogenesis of AD might be linked to insufficient clearance of amyloid deposits. These findings may open perspectives for new therapeutic strategies in AD.

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Catabolism of the human erythrocyte C3b/C4b receptor (CR1, CD35) : vesiculation and/or proteolysis?

Cited by 19 publications

References 45 publications

A human complement receptor 1 polymorphism that reducesPlasmodium falciparumrosetting confers protection against severe malaria

A human complement receptor 1 polymorphism that reducesPlasmodium falciparumrosetting confers protection against severe malaria

Mapping of Epitopes in Discoidin Domain Receptor 1 Critical for Collagen Binding

Inherited and Acquired Decrease in Complement Receptor 1 (CR1) Density on Red Blood Cells Associated with High Levels of Soluble CR1 in Alzheimer’s Disease

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