Phospholipid transfer activity of microsomal triacylglycerol transfer protein is sufficient for the assembly and secretion of apolipoprotein B lipoproteins.
Human microsomal triacylglycerol transfer protein (hMTP) is essential for apolipoprotein B (apoB)-lipoprotein assembly and secretion and is known to transfer triacylglycerols, cholesterol esters, and phospholipids. To understand the relative importance of each lipid transfer activity, we compared the ability of hMTP and its Drosophila ortholog (dMTP) to assemble apoB lipoproteins and to transfer various lipids. apoB48 secretion was induced when co-expressed with either hMTP or dMTP in COS cells, and oleic acid supplementation further augmented secretion without altering particle density. C-terminal epitope-tagged dMTP (dMTP-FLAG) facilitated the secretion of apoB polypeptides in the range of apoB48 to apoB72 but was approximately 50% as efficient as hMTP-FLAG. Comparison of lipid transfer activities revealed that although phospholipid transfer was similar in both orthologs, dMTP was unable to transfer neutral lipids. We conclude that the phospholipid transfer activity of MTP is sufficient for the assembly and secretion of primordial apoB lipoproteins and may represent its earliest function evolved for the mobilization of lipid in invertebrates. Identification of MTP inhibitors, which selectively affect transfer of a specific lipid class, may have therapeutic potential.
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
Paul
P
Rava
George K
GK
Ojakian
Gregory S
GS
Shelness
M Mahmood
MM
Hussain
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D002846:Chromatography, Affinity; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D000939:Epitopes / Q000737:chemistry; D017353:Gene Deletion; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry; D008856:Microscopy, Fluorescence; D019301:Oleic Acid / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D002352:Carrier Proteins; D002788:Cholesterol Esters; D000939:Epitopes; D008055:Lipids; D008074:Lipoproteins; D010455:Peptides; D010743:Phospholipids; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D019301:Oleic Acid; D002784:Cholesterol