Thioreductase activity of retina cognin and its role in cell adhesion.
Retina cognin (R-cognin) is a 50-kDa protein on the surface of embryonic chick retina cells that mediates cell-cell recognition and neuronal differentiation. It is developmental stage- and tissue-specific in its expression. The partial cDNA clone for R-cognin is nearly identical to that of chicken protein disulfide isomerase (chicken PDI) and enzyme with thioreductase activity. The R-cognin clone extends from beyond the 3' polyadenylation site up to the boundary between PDI exons 1 and 2, with the putative R-cognin equivalent of PDI exon 1 remaining uncloned. The question posed here was whether the sequence-specific properties of PDI were significant in the action of R-cognin. We show that R-cognin, like PDI, has thioreductase activity as revealed by RNase renaturation enzymatic assays. We then asked if this thioreductase activity was involved in the mediation of cell adhesion and recognition in developing chick retina. We show, through cell aggregation assays, that both R-cognin and chicken PDI enhance chick retina cell aggregation but not that of cells from other CNS tissues. We also show that treating R-cognin and chicken PDI with the thioreductase inhibitor 5,5'-dithio-bis (2-nitrobenzoic acid), which covalently binds to the functional cysteines of the thioreductase active sites, reduces the enhancement of cell aggregation. Thus R-cognin acts, in part, by catalyzing a covalent protein-protein linkage at the cell surface.
Pariser
H P
HP
Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Rakeman
A S
AS
Hausman
R E
RE
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002449:Cell Aggregation / Q000502:physiology; D002642:Chick Embryo; D016172:DNA Fingerprinting; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000502:physiology*
D008565:Membrane Proteins; C026097:cognin; D010088:Oxidoreductases; D019704:Protein Disulfide-Isomerases