The membrane receptors guanylyl cyclase-A and -B undergo distinctive changes in post-translational modification during brain development.
Temporal carbohydrate expression patterns at cell surfaces are thought to be of crucial regulatory significance during developmental processes. Hitherto, however, data on individual membrane proteins undergoing development-associated changes in glycosylation are sparsely. Here, we show that the two natriuretic peptide receptors, guanylyl cyclase-A (GC-A) and GC-B are subject to pronounced size alterations in the rat brain between postnatal day 1 and adult. Comparable size changes were not detectable for GC-A and GC-B in peripheral tissues and for three other membrane proteins (insulin receptor, insulin-like growth factor-II/mannose-6-phoshate receptor, neutral endopeptidase) in brain, indicating remarkable specificity. As revealed by treatments with carbohydrate-digesting enzymes, both GC-A and GC-B are hyperglycosylated at N-linked glycosylation sites in the developing brain. At postnatal day 1, the vast majority of GC-B (but not GC-A) molecules contain additionally an O-linked carbohydrate modification of about 1 kDa in mass and a further modification of similar size which is resistant to enzymatic removal. The glycoforms exhibited functional activity in membrane GC assays, indicating proper folding and signaling capability. These data link recently reported roles of natriuretic peptides during brain development for the first time with specific glycosylation states of their cyclic GMP-generating receptors.
Müller
Dieter
D
Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany. hans-dieter.mueller@anatomie.med.uni-giessen.de
Hildebrand
Mirjam
M
Lübberstedt
Jörn
J
Kuhn
Michaela
M
Middendorff
Ralf
R
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D006031:Glycosylation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D000099242:Atrial Natriuretic Factor Receptor B
D008565:Membrane Proteins; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C091715:atrial natriuretic factor receptor A