Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The subtilisin-like enzyme PC1 (also known as PC3) cleaves the neuropeptide precursor proopiomelanocortin at paired basic residues in transfection experiments, thus providing evidence for a critical role in precursor processing. While mRNA for this enzyme is highly enriched in neuroendocrine tissues, little is known about the tissue and subcellular distribution of the PC1 protein. This study used immunocytochemical techniques to investigate the anatomical distribution of PC1, both alone and compared to met-enkephalin (MET-enk), in AtT-20 pituicytes transfected with proenkephalin cDNA. A high density of PC1 immunostaining was observed in a small region adjacent to the nucleus and in the tips of the processes of these cells. Dual-staining immunocytochemistry of whole cells illustrated that both PC1 and MET-enk immunoreactivity were present in the tips, but PC1 was concentrated in a region adjacent to the nucleus while MET-enk punctate staining was dispersed throughout the soma. This codistribution was confirmed in semithin sections of dual-stained cells cut at 1-1.5 microns through the thickness of the cells. PC1 staining resembled that of TGN38, a marker for the trans-Golgi network. When PC1 immunocytochemistry was performed in cells that were pretreated with brefeldin A, a drug that redistributes the proximal Golgi compartments to the endoplasmic reticulum, there was a complete disruption of the defined locus of PC1 immunoreactivity. Taken together, our data indicate that (1) PC1 is concentrated in a region of the cell body resembling the trans-Golgi network and (2) both the enzyme and the processed peptide are transported to the tips of the processes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical localization of the neuropeptide-synthesizing enzyme PC1 in AtT-20 cells. 811 23

The formation of secretory granules and regulated secretion are generally assumed to occur only in specialized endocrine, neuronal, or exocrine cells. We discovered that regulated secretory proteins such as the hormone precursors pro-vasopressin, pro-oxytocin, and pro-opiomelanocortin, as well as the granins secretogranin II and chromogranin B but not the constitutive secretory protein alpha(1)-protease inhibitor, accumulate in granular structures at the Golgi and in the cell periphery in transfected COS-1 fibroblast cells. The accumulations were observed in 30-70% of the transfected cells expressing the pro-hormones and for virtually all of the cells expressing the granins. Similar structures were also generated in other cell lines believed to be lacking a regulated secretory pathway. The accumulations resembled secretory granules morphologically in immunofluorescence and electron microscopy. They were devoid of markers of the endoplasmic reticulum, endosomes, and lysosomes but in part stained positive for the trans-Golgi network marker TGN46, consistent with their formation at the trans-Golgi network. When different regulated proteins were coexpressed, they were frequently found in the same granules, whereas alpha(1)-protease inhibitor could not be detected in accumulations formed by secretogranin II, demonstrating segregation of regulated from constitutive secretory proteins. In pulse-chase experiments, significant intracellular storage of secretogranin II and chromogranin B was observed and secretion of retained secretogranin II was stimulated with the calcium ionophore A23187. The results suggest that expression of regulated cargo proteins is sufficient to generate structures that resemble secretory granules in the background of constitutively secreting cells, supporting earlier proposals on the mechanism of granule formation.
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PMID:Expression of regulated secretory proteins is sufficient to generate granule-like structures in constitutively secreting cells. 1499 40