N-glycosylation modulates the cell-surface expression and catalytic activity of corin.
N-glycosylation may influence the subcellular localization and biological activity of the pro-ANP convertase, corin. In HEK293-corin cells, the inhibition of N-glycosylation, with tunicamycin, reduced the cell-surface expression of murine corin, but did not alter the total expression. Therefore, tunicamycin treatment likely caused the intracellular accumulation of non-glycosylated corin. Tunicamycin treatment also significantly reduced corin activity (pro-ANP cleavage) in these cells. We developed an assay to measure the effect of N-glycosylation on corin activity, independent of its effect on corin localization. We determined that the reduction in corin activity was due to a direct effect of N-glycosylation, and was not secondary to the effect of N-glycosylation on corin cell-surface expression. Our data provide evidence that N-glycosylation is essential for the cell-surface expression of murine corin and modulates its functional activity. N-Glycosylation represents a possible mechanism for the regulation of native corin on the surface of cardiomyocytes.
Cardiovascular Research Center, Department of Medicine, Medical College of Georgia, 1120 15th Street, CB-2207, Augusta, GA 30912, USA. igladysheva@mcg.edu
Inna P
IP
Gladysheva
Sarah M
SM
King
Aiilyan K
AK
Houng
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000201:enzymology; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
D011994:Recombinant Proteins; D014415:Tunicamycin; D009320:Atrial Natriuretic Factor; C485617:Corin protein, mouse; D012697:Serine Endopeptidases