BIOSYNTHESIS AND DEGRADATION OF MEPRINS, KIDNEY BRUSH-BORDER PROTEINASES

Meprins, which are cell surface metalloendopeptidases, consist of two types of subunits, α and β. Genetic factors determine which subunits and oligomeric forms of the enzyme exist in kidney in different strains of mice. In order to further explore factors that determine the concentration and activity of meprins, the rates of biosynthesis and degradation of the meprin subunits were determined in an organ culture system using ICR and C3H/He mouse kidneys. In biosynthesis experiments, the rate of incorporation of radiolabeled amino acids into immunoprecipitable forms of the α and β subunits was determined. The rate of loss of radiolabel from the subunits was measured in pulse-chase experiments to determine the half-lives of the subunits. The rate of synthesis of the α subunit was twofold greater than that of the β subunit: 861 ± 32 vs 361 ± 23 dpm/μg subunit protein/min for α vs β. The rate of synthesis for total kidney protein in both strains was approximately 700 dpm/μg/min. The half-life for α was 8.9 ± 0.24 h compared to 12.1 ± 0.7 h for β; the half-life for total protein in kidney was approximately 35 h. Thus, the half-lives of α and β were similar and shorter than the half-lives of the average protein in kidney cells. The higher rate of synthesis of α is probably responsible for the greater abundance of this protein compared to β in microvillus membranes. © 1993 Academic Press, Inc.