The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20061568
The Journal of Experimental Medicine, Vol. 204, No. 4, 921-928
The Rockefeller University Press, 0022-1007 $30.00
© Sagiv et al.
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ARTICLE

 A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d

Yuval Sagiv1, Li Bai1, Datsen G. Wei1, Reuven Agami3, Paul B. Savage4, Luc Teyton5, and Albert Bendelac1,2

1 Committee on Immunology and 2 Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637
3 Division of Tumor Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands
4 Department of Chemistry, Brigham Young University, Provo UT 84602
5 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

CORRESPONDENCE Albert Bendelac: abendela{at}bsd.uchicago.edu

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.

Abbreviations used: GSL, glycosphingolipid; HEL, hen egg lyzozyme; HRP, horse radish peroxidase; KD, knock down; MTP, microsomal triglyceride transfer protein; RBL, rat basophilic leukemia; siRNA, small interfering RNA.


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