Biosynthesis and degradation of meprins, kidney brush border proteinases.
Meprins, which are cell surface metalloendopeptidases, consist of two types of subunits, alpha and beta. 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 alpha and beta 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 alpha subunit was twofold greater than that of the beta subunit: 861 +/- 32 vs 361 +/- 23 dpm/micrograms subunit protein/min for alpha vs beta. The rate of synthesis for total kidney protein in both strains was approximately 700 dpm/micrograms/min. The half-life for alpha was 8.9 +/- 0.24 h compared to 12.1 +/- 0.7 h for beta; the half-life for total protein in kidney was approximately 35 h. Thus, the half-lives of alpha and beta were similar and shorter than the half-lives of the average protein in kidney cells. The higher rate of synthesis of alpha is probably responsible for the greater abundance of this protein compared to beta in microvillus membranes.
Hall
J L
JL
Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond 23298-0614.
Sterchi
E E
EE
Bond
J S
JS
D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D007457:Iodine Radioisotopes; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D046911:Macromolecular Substances; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D008871:Microvilli / Q000201:enzymology*; D008970:Molecular Weight; D009924:Organ Culture Techniques; D013045:Species Specificity; D013462:Sulfur Radioisotopes
D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D013462:Sulfur Radioisotopes; D008715:Methionine; D008666:Metalloendopeptidases