Biosynthetic relationships between three rat apolipoprotein B peptides.
Rat liver is unique in secreting very low density lipoproteins (VLDL) with three size-isoforms of apolipoprotein B: PI and PIII correspond to B-100 and B-48, respectively, while PII is slightly smaller than PI and has no counterpart in other species. Antibodies against a fusion protein corresponding to the extreme C-terminal region of PI fail to react with PII, suggesting that the latter lacks this moiety. [35S]Methionine-labeled perfused rat liver and isolated hepatocytes secrete labeled PII, but intracellular apoB contains only PI and PIII. The absence of labeled PII from Golgi VLDL, and the absence of continued PII production within the plasma compartment, strongly suggest that PIII-containing VLDL are formed by a one-time proteolytic processing of a certain proportion of PI-containing VLDL at the time of secretion. In contrast, polysome run-off translation experiments and analysis of polysome-bound nascent apoB chains show that both rat liver and intestinal polysomes release PIII-sized peptides directly at the appropriate point of elongation, in a manner incompatible with their formation by posttranslational processing. These results strongly suggest that the large (PI, B-100) and small (PIII, B-48) apoB peptides are translated from separate mRNAs. Thus, although both PII and PIII are C-terminally truncated products of PI, the mechanisms involved are entirely different.
Reuben
M A
MA
Lipid Research, Veterans Administration, Wadsworth Medical Service, Los Angeles, CA 90073.
Svenson
K L
KL
Doolittle
M H
MH
Johnson
D F
DF
Lusis
A J
AJ
Elovson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D051381:Rats
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B