title: A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d.
abstract: Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)-resident lipid transfer protein involved in the biosynthesis and lipid loading of apolipoprotein B. MTP was recently suggested to directly regulate the biosynthesis of the MHC I-like, lipid antigen presenting molecule CD1d, based on coprecipitation experiments and lipid loading assays. However, we found that the major impact of MTP deficiency occurred distal to the ER and Golgi compartments. Thus, although the rates of CD1d biosynthesis, glycosylation maturation, and internalization from the cell surface were preserved, the late but essential stage of recycling from lysosome to plasma membrane was profoundly impaired. Likewise, functional experiments indicated defects of CD1d-mediated lipid presentation in the lysosome but not in the secretory pathway. These intriguing findings suggest a novel, unexpected role of MTP at a late stage of CD1d trafficking in the lysosomal compartment.
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Sagiv
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.forename: Datsen G
authors.initials: DG
authors.lastname: Wei
authors.forename: Reuven
authors.initials: R
authors.lastname: Agami
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism
chemical_list: D000941:Antigens; D018949:Antigens, CD1; D002352:Carrier Proteins; D008055:Lipids; C106092:microsomal triglyceride transfer protein