BIOSYNTHESIS OF PREPRORENIN AND INTRACELLULAR CONVERSION OF PRORENIN TO RENIN

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Abstract
1. The existence of a biosynthetic precursor of renin (prorenin) has been inferred, but never established experimentally. The aim of the present study was to provide this evidence. 2. In a continuous labelling experiment using submandibular glands of male Quackenbush mice (an extraordinarily rich source of renin) a molecule of Mr 44 500 was immunoprecipitated with antiserum to renin. 3. The Mr 44 500 protein was converted to Mr 40 000 renin in a time-dependent fashion during incubation of tissue at 37 degrees C: 15 min after addition of [35S] methionine only 16% of immunoprecipitable radioactivity was renin, whereas by 4 h this had increased to 86%. The Mr 44 500 protein would therefore appear to be a 'pro' form of renin. 4. Submandibular gland mRNA was translated in a cell-free system derived from rabbit reticulocyte lysate and a molecule of Mr 46 000 was immunoprecipitated with antirenin. This was preprorenin and the Mr of the 'pre' region would thus be 1500, which is consistent with the size generally found for the 'pre' region of secretory proteins. 5. The present study has therefore demonstrated for the first time the biosynthesis of a 'pro' form of renin (prorenin) and its conversion to renin intracellularly.