Palmitoylation of apolipoprotein B is required for proper intracellular sorting and transport of cholesteroyl esters and triglycerides.
Apolipoprotein B (apoB) is an essential component of chylomicrons, very low density lipoproteins, and low density lipoproteins. ApoB is a palmitoylated protein. To investigate the role of palmitoylation in lipoprotein function, a palmitoylation site was mapped to Cys-1085 and removed by mutagenesis. Secreted lipoprotein particles formed by nonpalmitoylated apoB were smaller and denser and failed to assemble a proper hydrophobic core. Indeed, the relative concentrations of nonpolar lipids were three to four times lower in lipoprotein particles containing mutant apoB compared with those containing wild-type apoB, whereas levels of polar lipids isolated from wild-type or mutant apoB lipoprotein particles appeared identical. Palmitoylation localized apoB to large vesicular structures corresponding to a subcompartment of the endoplasmic reticulum, where addition of neutral lipids was postulated to occur. In contrast, nonpalmitoylated apoB was concentrated in a dense perinuclear area corresponding to the Golgi compartment. The involvement of palmitoylation as a structural requirement for proper assembly of the hydrophobic core of the lipoprotein particle and its intracellular sorting represent novel roles for this posttranslational modification.
Zhao
Y
Y
Departments of Cell Biology and Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
McCabe
J B
JB
Vance
J
J
Berthiaume
L G
LG
D000818:Animals; D001055:Apolipoproteins B / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002788:Cholesterol Esters / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D019811:Hydroxylamine / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017384:Sequence Deletion / Q000235:genetics; D013329:Structure-Activity Relationship; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008055:Lipids; D008077:Lipoproteins, LDL; D014280:Triglycerides; D019811:Hydroxylamine; D019308:Palmitic Acid; D003545:Cysteine