Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 204, Issue 4, Pages 921-928Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20061568
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Funding
- NIAID NIH HHS [P01 AI053725] Funding Source: Medline
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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.
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