A role for palmitoylation in the quality control, assembly and secretion of apolipoprotein B.
ApoB (apolipoprotein B)-containing lipoprotein particles, such as chylomicrons, very-low-density and low-density lipoprotein particles, transport triacylglycerol and cholesteryl esters in the bloodstream. A palmitoylation site was previously mapped to Cys-1085 in a functional truncated apoB variant (apoB-29) and abolished by mutagenesis. This Cys-1085Ser mutation resulted in secretion of smaller and denser lipoprotein particles containing 80% less cholesteryl ester and triacylglycerol than wild-type controls. We show that palmitoylation of apoB-29 occurs in the ER (endoplasmic reticulum), stimulates the ER-Golgi transport rate of apoB-29 almost 2-fold, doubles the secretion efficiency of wild-type apoB-29 in comparison with (Cys-1085Ser)apoB-29 and reduces significantly the association of wild-type apoB-29 with calnexin in comparison with (Cys-1085Ser)apoB-29. While non-palmitoylated apoB-29 co-localized extensively with constitutively secreted transferrin, wild-type apoB-29 did so only partially and was enriched in ER extensions. Our results suggest that palmitoylation of apoB regulates the biogenesis of nascent apoB-containing lipoprotein particles by concentrating apoB in a specialized ER compartment and by stimulating dissociation from constituents of the ER quality-control machinery. This reduced interaction would lead to a faster ER-Golgi transit time and a higher secretion efficiency of wild-type apoB-29. Palmitoylation could regulate the amount of apoB available for secretion of neutral lipids.
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003545:Cysteine / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D006056:Golgi Apparatus / Q000737:chemistry; D006801:Humans; D009154:Mutation; D010169:Palmitic Acids / Q000378:metabolism*; D017510:Protein Folding; D051381:Rats
D001055:Apolipoproteins B; D010169:Palmitic Acids; D003545:Cysteine