| First Author | De Bie I | Year | 1996 |
| Journal | J Cell Biol | Volume | 135 |
| Issue | 5 | Pages | 1261-75 |
| PubMed ID | 8947550 | Mgi Jnum | J:37018 |
| Mgi Id | MGI:84424 | Doi | 10.1083/jcb.135.5.1261 |
| Citation | De Bie I, et al. (1996) The isoforms of proprotein convertase PC5 are sorted to different subcellular compartments. J Cell Biol 135(5):1261-75 |
| abstractText | The proprotein convertase PC5 is encoded by multiple mRNAs, two of which give rise to the COOH-terminal variant isoforms PC5-A (915 amino acids [aa]) and PC5-B (1877 aa). To investigate the differences in biosynthesis and sorting between these two proteins, we generated stably transfected AtT-20 cell lines expressing each enzyme individually and examined their respective processing pattern and subcellular localization. Biosynthetic analyses coupled to immunofluorescence studies demonstrated that the shorter and soluble PC5-A is sorted to regulated secretory granules. In contrast, the COOH-terminally extended and membrane-bound PC5-B is located in the Golgi. The presence of a sorting signal in the COOH-terminal 38 amino acids unique to PC5-A was demonstrated by the inefficient entry into the regulated secretory pathway of a mutant lacking this segment. EM of pancreatic cells established the presence of immunoreactive PC5 in glucagon-containing granules, demonstrating the sorting of this protein to dense core secretory granules in endocrine cells. Thus, a single PC5 gene generates COOH-terminally modified isoforms with different sorting signals directing these proteins to distinct subcellular localization, thereby allowing them to process their appropriate substrates. |
