Biosynthesis of renin: multiplicity of active and intermediate forms.
Processing of renin involves sequential proteolytic cleavages of a preproform to the active mature forms. Preprorenin is rapidly internalized cotranslationally into the rough endoplasmic reticulum and hydrolyzed by signal peptidase to produce prorenin. In the Golgi, prorenin is converted (within 15 min) to a form of renin that is enzymatically active. Over the next 12 hr, a slow intracellular process removes a dipeptide near the carboxyl terminus, converting the one-chain renin into two chains joined by a single disulfide bond. This conversion occurs during formation, condensation, and packaging of renin granules. The resultant two-chain renin is approximately one-sixth as active as the one-chain form. The intact renin molecule is obligatory for enzymatic activity because heavy chain alone has little or no activity. Both one- and two-chain renins are secreted, but prorenin is not. Multiple isoelectric forms of prorenin, one-chain renin, and two-chain renin are also observed. This microheterogeneity probably results from minor differences in amino acid composition as a consequence of variations in cleavage positions during processing. Thus, these data suggest that renin synthesis and secretion is complex and may be subject to regulation at multiple steps. Furthermore, based on the results of this study, we also propose that renin can be secreted by two different pathways.
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000378:metabolism; D008970:Molecular Weight; D010179:Pancreas / Q000378:metabolism; D011061:Poly A / Q000235:genetics; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D012083:Renin / Q000235:genetics* / Q000302:isolation & purification; D012156:Reticulocytes / Q000378:metabolism; D013363:Submandibular Gland / Q000201:enzymology*
D012333:RNA, Messenger; D011061:Poly A; D012083:Renin