Expression and conservation of apolipoprotein AIV in an avian species.
In birds, intestinally derived lipoproteins are thought to be secreted directly into the portal vein rather than to enter the circulation via the lymphatic system as in mammals. Hepatic clearance of these so-called portomicrons must be rapid, but the protein(s) mediating their catabolism, presumably analogues of the 36-kDa mammalian apolipoprotein E, have not been identified. In searching for such a mediator(s), we have isolated a hitherto unknown 38-kDa protein from chicken serum, which we identified by microsequencing and molecular cloning as a counterpart to mammalian apolipoprotein AIV (apoAIV). Mature chicken apoAIV consists of 347 amino acids, lacks cysteine residues, and displays 57% sequence identity with human apoAIV and, to a significantly lesser extent, with apoAIVs of rodents. This first nonmammalian apoAIV characterized is the smallest homologue reported so far, because of the lack of repeated motifs at the carboxyl terminus with the consensus sequence Glu-Gln-Glu/Ala-Gln, a hallmark of mammalian apoAIVs. Chicken apoAIV (isoelectric point, 4.65) is also considerably more acidic than its human counterpart. Agarose gel electrophoresis revealed that unlike human apoAIV, which migrates to a pre-alpha-position, chicken apoAIV shows fast alpha migration. Functional characterization demonstrated that the avian protein is able to activate the enzyme lecithin:cholesterol acyltransferase. Roosters and hens express apoAIV predominantly in the gut, one-fifth as much in the liver, and no other sites of expression are identifiable by Northern blot analysis. Although pronounced intestinal synthesis is common to apoAIVs, the features of the avian protein support the notion that it represents a prototype of an apoprotein that evolved to acquire possibly distinct functions in mammals and birds.
Steinmetz
A
A
Department of Molecular Genetics, University and Biocenter Vienna, A-1030 Vienna, Austria.
Hermann
M
M
Nimpf
J
J
Aebersold
R
R
Ducret
A
A
Weinberg
R B
RB
Schneider
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics*; D001483:Base Sequence; D002645:Chickens; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D002785:Sterol O-Acyltransferase / Q000235:genetics
D001054:Apolipoproteins A; D018076:DNA, Complementary; C022205:apolipoprotein A-IV; D002785:Sterol O-Acyltransferase