Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly

The microsomal triglyceride transfer protein (MTP) is necessary for the pro per assembly of the apolipoprotein B containing lipoproteins, very low dens ity lipoprotein and chylomicrons. Recent research has significantly advance d our understanding of the role of MTP in these pathways at the molecular a nd cellular level. Biochemical studies suggest that initiation of lipidatio n of the nascent apolipoprotein B polypeptide may occur through a direct as sociation with MTP. This early lipidation may be required to allow the nasc ent polypeptide to fold properly and therefore avoid ubiquitination and deg radation. Concerning the addition of core neutral lipids in the later stage s of lipoprotein assembly, cell culture studies show that MTP lipid transfe r activity is not required for this to occur for apolipoprotein B-100 conta ining lipoproteins. Likewise, MTP does not appear to directly mediate addit ion of core neutral lipid to nascent apoB-48 particles. However, new data i ndicate that MTP is required to produce triglyceride rich droplets in the s mooth endoplasmic reticulum which may supply the core lipids for conversion of nascent, dense apoB-48 particles to mature VLDL. In addition, assembly of dense apolipoprotein B-48 containing lipoproteins has been observed in m ouse liver in the absence of MTP. As a result of these new data, an updated model for the role of MTP in lipoprotein assembly is proposed. (C) 2000 El sevier Science B.V. All rights reserved.