Selective Expression of a Subset of Measles Virus Receptor-Competent CD46 Isoforms in Human Brain

Buchholz, Christian J.; Gerlier, Denis; Hu, Aizhong; Cathomen, Toni; Liszewski, M. Kathryn; Atkinson, John P.; Cattaneo, Roberto

doi:10.1006/viro.1996.0122

Cited by 40 publications

(38 citation statements)

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“…The upper band predominant pattern was observed in liver, lung, spleen and ovary as it was in most other tissues (Table 1). In addition, tissuespecific expression of the BC2 isoform in the kidney, the C2 isoform in the brain [29], and the BC2 isoform in the salivary gland paralleled that found in humans [30,31].…”

Section: Resultsmentioning

confidence: 67%

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Kemper

Leung

Stephensen

et al. 2001

Clinical and Experimental Immunology

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SUMMARYHuman membrane cofactor protein (MCP; CD46) is a widely distributed complement regulator. In the mouse, expression of MCP is largely restricted to the testis while a related, widely expressed protein (Crry) appears to perform MCP's (CD46) regulatory activity. We have developed two mouse strains transgenic for human MCP (CD46) utilizing an , 400 kb YAC clone carrying the complete gene. A third mouse strain was generated using an overlapping YAC clone isolated from a second library. The expression of human MCP (CD46) in these mouse strains was characterized by immunohistochemistry, FACS, Western blotting and RT-PCR. No differences were detected in the isoform pattern or distribution among the three strains, although the expression level varied according to how many copies of the gene were integrated. The expression profile closely mimicked that observed in humans, including the same pattern of isoform expression as the donor. In addition, tissue-specific isoform expression in the kidney, salivary gland and brain paralleled that observed in man. The transgenic mice expressed low levels of MCP (CD46) on their E, in contrast to humans but in line with most other primates. These mice should be a useful tool to analyse tissue-specific expression, to establish animal models of infections and to characterize the role of MCP (CD46) in reproduction.

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Section: Resultsmentioning

confidence: 67%

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Kemper

Leung

Stephensen

et al. 2001

Clinical and Experimental Immunology

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“…MCP isoforms are named on the basis of their STP and tail domains (i.e., BC1, BC2, C1, and C2). While most cells in a given individual express the same ratio of MCP isoforms, one prominent exception is the brain, where MCP bearing CYT-2 is preferentially expressed (32,33).…”

Section: Embrane Cofactor Protein (Mcp)mentioning

confidence: 99%

Membrane Cofactor Protein (MCP; CD46): Isoform-Specific Tyrosine Phosphorylation

Wang

Liszewski

Chan

et al. 2000

The Journal of Immunology

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Membrane cofactor protein (MCP; CD46) is a widely expressed type 1 transmembrane glycoprotein that inhibits complement activation on host cells. It also is a receptor for several pathogens including measles virus, Streptococcus pyogenes, Neisseria gonorrhea, and Neisseria meningitidis. That MCP may have signaling capability was suggested by its microbial interactions. That is, binding of MCP on human monocytes by measles virus hemagglutinin or cross-linking by an anti-MCP Ab resulted in IL-12 down-regulation, while binding to MCP by Neisseria on epithelial cells produced a calcium flux. Through alternative splicing, MCP is expressed on most cells with two distinct cytoplasmic tails of 16 (CYT-1) or 23 (CYT-2) amino acids. These play pivotal roles in intracellular precursor processing and basolateral localization. We investigated the putative signal transduction pathway mediated by MCP and demonstrate that CYT-2, but not CYT-1, is phosphorylated on tyrosine. We examined MCP tail peptides and performed Ab cross-linking experiments on several human cell lines and MCP isoform transfectants. We found an MCP peptide of CYT-2 was phosphorylated by a src kinase system. Western blots of the cells lines demonstrated that cells bearing CYT-2 were also phosphorylated on tyrosine. Additionally, we provide genetic and biochemical evidence that the src family of kinases is responsible for the latter phosphorylation events. In particular, the src kinase, Lck, is required for phosphorylation of MCP in the Jurkat T cell line. Taken together, these studies suggest a src family-dependent pathway for signaling through MCP.

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“…The corresponding protein (6, Fig. 4 Buchholz et al, 1996b), and for protein 6, to those of the CD46 isoform C2 (Buchholz et al, 1996a). The number of plus signs indicates the level: ++ + corresponds to 71-130% of the standard level; ++, 31-70%; +, 10-30%; -, less than 10%.…”

Section: Protein Segments Essential For Jrnctionmentioning

confidence: 99%

“…Transient expression of standard and mutant CD46 proteins was in mouse Ltk-cells with the vTF7-3 system (Buchholz et al, 1996a). Protein analysis was as described (Buchholz et ai., 1996b), by western blotting, fluorescence-activated cell sorter analysis using the appropriate antibodies, or by the cell-cell fusion assay.…”

Section: Transient Expression Of Mutant Proteinsmentioning

confidence: 99%

A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

et al. 1997

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The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 CCP modules are about 35 8, long, and form a five-stranded antiparallel P-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-11. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the viral hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-1-11 interface region.

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Selective Expression of a Subset of Measles Virus Receptor-Competent CD46 Isoforms in Human Brain

Cited by 40 publications

References 0 publications

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Membrane Cofactor Protein (MCP; CD46): Isoform-Specific Tyrosine Phosphorylation

A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

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