title: Loss of both phospholipid and triglyceride transfer activities of microsomal triglyceride transfer protein in abetalipoproteinemia.
abstract: Mutations in microsomal triglyceride transfer protein (MTP) cause abetalipoproteinemia (ABL), characterized by the absence of plasma apoB-containing lipoproteins. In this study, we characterized the effects of various MTP missense mutations found in ABL patients with respect to their expression, subcellular location, and interaction with protein disulfide isomerase (PDI). In addition, we characterized functional properties by analyzing phospholipid and triglyceride transfer activities and studied their ability to support apoB secretion. All the mutants colocalized with calnexin and interacted with PDI. We found that R540H and N780Y, known to be deficient in triglyceride transfer activity, also lacked phospholipid transfer activity. Novel mutants S590I and G746E did not transfer triglycerides and phospholipids and did not assist in apoB secretion. In contrast, D384A displayed both triglyceride and phospholipid transfer activities and supported apoB secretion. These studies point out that ABL is associated with the absence of both triglyceride and phospholipid transfer activities in MTP.
authors.affiliation: Molecular and Cellular Biology Program, SUNY Downstate Medical Center, Brooklyn, NY; School of Graduate Studies, Department of Cell Biology, and SUNY Downstate Medical Center, Brooklyn, NY; Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Irani
authors.initials: I
authors.lastname: Khatun
authors.affiliation: Molecular and Cellular Biology Program, SUNY Downstate Medical Center, Brooklyn, NY; School of Graduate Studies, Department of Cell Biology, and SUNY Downstate Medical Center, Brooklyn, NY; Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Meghan T
authors.initials: MT
authors.lastname: Walsh
authors.affiliation: School of Graduate Studies, Department of Cell Biology, and SUNY Downstate Medical Center, Brooklyn, NY; Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY. Electronic address: Mahmood.Hussain@downstate.edu.
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
mesh_terms: D000012:Abetalipoproteinemia / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D001693:Biological Transport, Active / Q000235:genetics; D019556:COS Cells; D037281:Calnexin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D020125:Mutation, Missense; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D002352:Carrier Proteins; D010743:Phospholipids; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D037281:Calnexin; D019704:Protein Disulfide-Isomerases
keywords: apolipoprotein B; lipoproteins; mutations