Evidence for rapid turnover of hepatic endoplasmic reticulum and its possible relationship to secretion.

Rat liver microsomal membranes were purified in order to remove membrane-associated secretory products. Measurements of the decay of the newly synthesized protein of these membranes in vivo were carried out at short time intervals after the protein was labeled by the administration of radioactive leucine. The result of these measurements suggest that the membranes are synthesized and degraded at approximately the same rapid rate as the synthesis and secretion of membrane-associated secretory products. Evidence that the highly dynamic protein of the purified membranes is indeed membrane protein is provided by the observations indicating: that this protein is immunochemically distinct from serum proteins, which are the major secretory product of liver; that many different protein components of the membranes turn over at similarly rapid rates; and that the biosynthesis of these proteins is specifically stimulated by the administration of phenobarbital, which is known to stimulate biosynthesis of hepatic endoplasmic reticulum. These findings suggest that in liver, as had been proposed earlier for the myeloma cell, unidirectional membrane flow, accompanied by rapid synthesis at the origin of flow and rapid degradation of the membranes at or near the terminus of flow, may be the mechanism for the intracellular transport of secretory product.