The cell adhesion molecule retina cognin is a cell surface protein disulfide isomerase that uses disulfide exchange activity to modulate cell adhesion.
The retina cell adhesion molecule, R-cognin, shares cDNA sequence with protein disulfide isomerase (PDI) but has a different molecular size and subcellular location. We asked whether R-cognin originated from a unique PDI gene transcript or was a product of posttranscriptional processing. The 3'-terminal partial cDNA clone for R-cognin was extended by both 5' RACE and by PCR from sequence near the 5' end of the PDI-translated region. The cDNA sequence was compared to those of chicken, bovine, and human PDI. The R-cognin cDNA sequence was identical to that of chicken PDI and differed by less than 10% from mammalian PDI proteins. The role of the disulfide exchange activity characteristic of both proteins was studied by assessing the cell-aggregation-enhancing ability and tissue specificity of R-cognin and recombinant human PDI and its derivatives. Chicken and normal human PDI proteins showed tissue- and developmental-specific enhancement of cell aggregation identical to R-cognin, and this activity was blocked by inactivation of the -WCGHC- motifs which function in disulfide exchange. Dependence of retina cell aggregation on disulfide exchange activity was shown by blocking that activity with the inhibitor, DTNB, or with a recombinant human PDI with the -WCGHC- motif cysteines mutated. The results suggest that one -WCGHC- motif in R-cognin is sufficient and that the more C-terminal motif is most active. We conclude that R-cognin is a tissue-specific protein product of the standard PDI chicken gene. The -WCGHC- motif in mature R-cognin is necessary, but not sufficient, for cell adhesion.
Department of Biology, Boston University, Massachusetts 02215, USA.
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Pariser
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Zhang
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Hausman
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002449:Cell Aggregation; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D011994:Recombinant Proteins; C026097:cognin; D019704:Protein Disulfide-Isomerases