title: The ins (cell) and outs (plasma) of apolipoprotein A-V.
abstract: 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.
authors.affiliation: Center for Prevention of Obesity, Diabetes, and Cardiovascular Disease, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. tforte@chori.org
authors.forename: Trudy M
authors.initials: TM
authors.lastname: Forte
authors.forename: Xiao
authors.initials: X
authors.lastname: Shu
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D001692:Biological Transport; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D014280:Triglycerides