title: A protease processing site is essential for prorenin sorting to the regulated secretory pathway.
abstract: Transfected mouse pituitary AtT-20 cells were used to examine the sorting of human prorenin to dense core secretory granules and the regulated secretory pathway. These cells secrete prorenin constitutively and sort a portion of the prorenin to secretory granules, where it is converted to active renin by proteolytic processing. Pulse-chase labeling of transfected AtT-20 cells demonstrated that regulated secretion of prorenin was prevented by: 1) the mutagenic deletion of the prosegment, 2) the premature proteolytic removal of the prosegment by a Golgi-resident processing protease, or 3) the mutation of the native cleavage site so as to prevent removal of the prosegment. In addition, expression of fusion proteins containing portions of the prorenin prosegment demonstrated that exposure of potential proteolytic cleavage sites was sufficient to confer cleavage-dependent regulated secretion of the corresponding protein. These data implicate the protease cleavage event in the regulated secretion of prorenin and are consistent with the involvement of a subclass of processing proteases in the sorting of certain proteins to secretory granules in AtT-20 cells.
authors.affiliation: Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal (IRCM), Montreal, Quebec H2W 1R7, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Brechler
authors.forename: W N
authors.initials: WN
authors.lastname: Chu
authors.forename: J D
authors.initials: JD
authors.lastname: Baxter
authors.forename: G
authors.initials: G
authors.lastname: Thibault
authors.forename: T L
authors.initials: TL
authors.lastname: Reudelhuber
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012083:Renin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D004792:Enzyme Precursors; D011993:Recombinant Fusion Proteins; D012083:Renin