Secretion of sulfated and nonsulfated forms of parathyroid chromogranin A (secretory protein-I).
Chromogranin A (secretory protein-I) is an acidic, sulfated glycoprotein found in secretory granules of most endocrine cells but not in exocrine or epithelial cells. Parathyroid chromogranin A is sulfated on tyrosine residues, whereas adrenal chromogranin A appears to be sulfated mainly on oligosaccharide residues. Chromogranin B, on the other hand, is tyrosine-sulfated in the bovine adrenal whereas this protein is absent from the parathyroid. The role of this tissue- or species-specific sulfation of chromogranin is not known. Tyrosine sulfation is a common post-translational modification of proteins in the exocytotic pathway and has been suggested to play a role in the sorting or intracellular transport of secretory proteins. To test this, porcine parathyroid tissue slices were metabolically labeled with 35SO4 and [3H]Lys, and the tissue and incubation medium analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and immunoprecipitation with chromogranin A-specific antiserum or by radioimmunoassay for parathormone. Secretion of total and 3H-labeled chromogranin A was about 3- and 7-fold higher, respectively, at 0.5 mM than at 3.0 mM Ca2+, and secretion of 35SO4-labeled chromogranin A was 67-fold higher. This indicates that either sulfated chromogranin A is directed primarily to the Ca2+-regulated pathway or that sulfation occurs following sorting to this pathway. Sodium chlorate (1-10 mM) inhibited sulfation in a dose-dependent manner by up to 95% but it had no effect on the onset or rate of chromogranin A secretion. These data indicate that regulated secretion of parathyroid chromogranin A does not require sulfation of tyrosine residues.
Gorr
S U
SU
Department of Oral Health, University of Louisville, Kentucky 40292.
Cohn
D V
DV
D000818:Animals; D001345:Autoradiography; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010280:Parathyroid Glands / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013464:Sulfuric Acids / Q000032:analysis; D013552:Swine; D014316:Tritium
D002135:Calcium-Binding Proteins; D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D013464:Sulfuric Acids; D014316:Tritium; D008239:Lysine