The isoforms of proprotein convertase PC5 are sorted to different subcellular compartments.
The Journal of cell biology, 1996•rupress.org
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 …
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 …
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.
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