SORTING AND SECRETION OF ADRENOCORTICOTROPIN IN A PITUITARY-TUMOR CELL-LINE AFTER PERTURBATION OF THE LEVEL OF A SECRETORY GRANULE-SPECIFIC PROTEOGLYCAN

A mouse anterior pituitary tumor cell line (AtT-20) that secretes ACTH and .beta. endorphin sorts the proteins it transports to the surface into 2 exocytotic pathways. AtT-20 cells also synthesize a secretory granule-specific sulfated molecule and secrete it on stimulation. This molecule is sensitive to proteolysis and the residual sulfated material co-migrates with a chondroitin sulfate standard on thin-layer electrophoresis. This sulfated molecule is completely sensitive to chondroitinase ABC digestion. Thus the secretory granule-specific sulfated molecule is a proteoglycan with chondroitin sulfate side chains. The role of proteoglycans in the sorting and secretion of ACTH in AtT-20 cells by severely decreasing the amount of this vesicle-specific proteoglycan in 2 ways. A xyloside was used to inhibit proteoglycan biosynthesis; 2nd, a variant of the AtT-20 cell line was isolated that synthesized little of the sulfated proteoglycan. In neither case was the sorting or secretion of ACTH detectably altered, suggesting that the proteoglycan is not required for these processes.