The ins (cell) and outs (plasma) of apolipoprotein A-V

Apolipoprotein A-V (apoA-V) has a close interrelationship with plasma triglyceride (TG). Since the discovery of the apoA-V gene in 2001, we have learned that single nucleotide polymorphisms in this gene correlate with altered plasma TG levels in humans, while genetically engineered mice manifest uni...

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Bibliographic Details
Published in:Journal of lipid research 2009-04, Vol.50 (Suppl), p.S150-S155
Main Authors: Forte, Trudy M., Shu, Xiao, Ryan, Robert O.
Format: Article
Language:English
Subjects:
Animals
apolipoprotein A-V intracellular trafficking
apolipoprotein A-V lipid binding
apolipoprotein A-V lipid droplet association
apolipoprotein A-V molecular structure
apolipoprotein A-V mutants
Apolipoproteins A - chemistry
Apolipoproteins A - metabolism
Atherosclerosis - metabolism
Biological Transport
Extracellular Space - metabolism
heparan sulfate proteoglycans
Humans
Intracellular Space - metabolism
Lipoprotein Metabolism
Triglycerides - metabolism
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Summary:Apolipoprotein A-V (apoA-V) has a close interrelationship with plasma triglyceride (TG). Since the discovery of the apoA-V gene in 2001, we have learned that single nucleotide polymorphisms in this gene correlate with altered plasma TG levels in humans, while genetically engineered mice manifest unique TG phenotypes. Studies of recombinant apoA-V protein have revealed that it is composed of two independently folded structural domains. The C-terminal domain possesses high lipid binding affinity, while the N-terminal domain adopts a helix bundle molecular architecture. A sequence element with high positive charge character, between residues 185 and 228, functions in binding of apoA-V to heparan sulfate proteoglycans as well as to members of the low-density lipoprotein receptor family and glycosylphosphatidylinositol high-density lipoprotein binding protein1. These interactions may be related to the capacity of this protein to regulate TG levels. ApoA-V is poorly secreted from transfected cultured hepatoma cell lines and is present in plasma at exceedingly low levels. Studies of apoA-V intracellular trafficking revealed an association with cytosolic lipid droplets. Thus, it is conceivable that apoA-V may also modulate TG metabolism within the cell. Much remains to be learned about this fascinating yet confounding member of the class of exchangeable apolipoproteins.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.R800050-JLR200