Palmitoylation of apolipoprotein B is required for proper intracellular sorting and transport of cholesteroyl esters and triglycerides

• Published in: Molecular biology of the cell 2000-02, Vol.11 (2), p.721-734
• Main Authors: Zhao, Y, McCabe, J B, Vance, J, Berthiaume, L G
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins B - chemistry; Apolipoproteins B - genetics; Apolipoproteins B - metabolism; Apolipoproteins B - secretion; Biological Transport; Cholesterol Esters - metabolism; Chromatography, Thin Layer; Cysteine - genetics; Cysteine - metabolism; Endoplasmic Reticulum - metabolism; Fluorescent Antibody Technique, Indirect; Golgi Apparatus - metabolism; Humans; Hydroxylamine - metabolism; Lipids - analysis; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - metabolism; Mutagenesis, Site-Directed; Palmitic Acid - metabolism; Protein Processing, Post-Translational; Rats; Sequence Deletion - genetics; Structure-Activity Relationship; Transfection; Triglycerides - metabolism; Tumor Cells, Cultured
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.11.2.721

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.