Abstract
Abstract The turnover of the protein constituents of the endoplasmic reticulum and certain cell fractions of rat liver has been examined by following the decay in specific radioactivity after a single administration of either uniformly labeled 14C-l-arginine or 14C-guanidino-l-arginine. Significantly shorter half-lives were obtained for all cell fractions when proteins were pulse-labeled with the guanidino-labeled arginine. The mean half-life for both rough and smooth microsomal membrane fractions was 2.0 to 2.1 days with guanidino-labeled arginine compared to 5.2 to 5.8 days with uniformly labeled arginine. We ascribe such differences to differing degrees of isotope reutilization. A new technique using two administrations of the same amino acid but labeled with different isotopes was developed to examine relative rates of degradation of proteins of the microsomal membranes. Proteins of the membrane, including NADPH-cytochrome c reductase, cytochrome b5, and protein fractions solubilized by detergent and separated on diethylaminoethyl-cellulose, had different rates of degradation. The administration of phenobarbital to rats induces proliferation of endoplasmic reticulum in the liver. Phenobarbital increased the rate of synthesis of some but not all proteins of the endoplasmic reticulum. The rate of synthesis of NADPH-cytochrome c reductase was increased 3- to 4-fold over the basal rate; the rate of cytochrome b5 synthesis was increased to an insignificant extent. The rate of synthesis of some membrane proteins was decreased during phenobarbital administration. Phenobarbital had no effect on the rate of degradation of total membrane protein. These results indicate that the endoplasmic reticulum is a dynamic system with a rapid rate of renewal and are consistent with a mosaic model of membrane biogenesis.
Highlights
The turnover of the protein constituents of the endoplasmic reticulum and certain cell fractions of rat liver has been for biochemicalreactionsand for compartmentalizationand intracellular transport of macromoleculesis well established[2]
Rather than being inert and constant in its constituents, the endoplasmicreticulum is a dynamic structure whoseconstituents and enzyme activities are continually changing. This is indicatedin part by the rapid responseosf residentenzymeactivities proteins were pulse-labeled with the guanidino-labeled arginine
Various investigators have presented a simplified formulation to describe the relationship between synthesis and degradation in determining the level of a protein or enzyme as follows [13,14,15] : These results indicate that the endoplasmicreticulum is a dE/dt = k, - kdE
Summary
The turnover of the protein constituents of the endoplasmic reticulum and certain cell fractions of rat liver has been for biochemicalreactionsand for compartmentalizationand intracellular transport of macromoleculesis well established[2]. Our major conclusions are (a) proteins of the endoplasmic reticulum are in a state of rapid turnover with a mean half-life of 2 days; [6] there is a heterogeneity of degradation rate constants among membrane proteins; (c) the effect of phenobarbital in increasing the level of protein constituents of the endoplasmic reticulum can be ascribed largely to accelerated rates of synthesis of some, but not all, membrane proteins. Because in all cases studied, except for that of the red blood cell and its hemoglobin [16]) the rate-of degradation of an individual intracellular motein has followed first order kinetics This ineludes the decay of enzyme activity after that activity has been increased to a high level by treatment with various agents (14,16; see 17), as well as the decay of specific, pulse-labeled proteins under conditions where the total amount of enzyme remains constant, i.e. a steady state (B-21). When we use the term rate of degradation, we are speaking of the rate constant of degradation
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