SUBCELLULAR-DISTRIBUTION AND MOLECULAR HETEROGENEITY OF ALPHA-1-FETOPROTEIN IN NEWBORN RAT-LIVER

Livers from 12 day old rats were subfractionated into nuclei, mitochondria, polyribosomes, rough microsomes, smooth microsomes, Golgi complex, and plasma membranes. The purity of the subcellular fractions was established from the specific activities of marker enzymes. The concentrations of a!-fetoprotein (AFP) were found to be highest in rough and smooth microsomes and in the Golgi complex. The ratio of albumin to AFP in serum was 15.8 to 1, whereas the ratio was a constant 7.3 to 1 for each of the secretory organelles; this 2.2-fold difference between the albumin/AFP ratios of serum and subcellular fractions seems referable to a 2.2-fold difference in their serum half-lives. These observations indicate that AFP follows the secretory pathway generally recognized for liver export proteins [Palade, G. (1975) Science 189, 347-358] and point to parallel dynamics of secretion of AFP and albumin. Polysomal AFP did not interact with conca-navalin A (Con A)-Sepharose, whereas rough microsomal AFP was 93% Con A reactive. The Con A reactivity of AFP in the Golgi complex and plasma membranes was similar to that of serum AFP (62% reactive). Rough microsomal AFP had a slower electrophoretic mobility than serum AFP. These observations can be explained by sequential glycosylation reactions occurring in subcellular compartments during secretion. Our data permit the drawing of a scheme for the processing of AFP in the liver cell and provide new insight into the biochemical significance of AFP molecular variants. They also indicate that, in the rat, the subcellular liver functions for the production, secretion, and processing of export peptides develop into an adult-type pattern early in the postnatal development. © 1979, American Chemical Society. All rights reserved.