Central nervous system-specific glycosylation of the type A natriuretic peptide receptor.
Physiological effects of atrial natriuretic peptide (ANP) are thought to be mediated by binding to and activation of a widely expressed membrane receptor, termed guanylyl cyclase (GC)-A. During comparative analyses of ANP receptor expression in various rat and bovine tissues, by UV light-induced affinity cross-linking to (125)I-ANP, we uncovered a size heterogeneity of GC-A, detectable as a 130-kDa protein in peripheral and as a 122-kDa protein in central nervous system tissues. This heterogeneity could be explained by differences in N-linked glycosylation, because treatments with N-glycosidase F reduced the apparent molecular weights of both receptor variants to the same value of 116,000. As judged by displacement experiments, the two receptor glycoforms did not differ in their binding affinities for natriuretic peptides. Assessments of GC activities did not reveal any difference in ANP-induced generation of the second messenger, cyclic GMP. The examination of GC-A expression in brain during ontogeny revealed an alteration of the apparent molecular mass during early postnatal development from the 130-kDa to the 122-kDa form, suggesting a change in oligosaccharide processing. This study provides a reliable method for characterizing GC-A expression and identifies, for the first time, a differential glycosylation of this receptor in vivo.
Müller
Dieter
D
Institute for Hormone and Fertility Research, University of Hamburg, Grandweg 24, 22529 Hamburg, Germany. mueller@ihf.de
Middendorff
Ralf
R
Olcese
James
J
Mukhopadhyay
Amal K
AK
D000375:Aging / Q000378:metabolism; D000581:Amidohydrolases / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002490:Central Nervous System / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006031:Glycosylation; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D020033:Protein Isoforms / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects
D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A