Subcellular localization of microsomal triglyceride transfer protein (MTP)

Larry L. Swift, Mei-Ying Zhu, Bharati Kakkad, Aneta Jovanovska, M. Diana Neely, Klara Valyi-Nagy, Richard L. Roberts, David E. Ong, and W. Gray Jerome

Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-2561

Corresponding Author: larry.swift{at}vanderbilt.edu

Microsomal triglyceride transfer protein (MTP) is essential for assembly of apoB-containing lipoproteins. Within the endoplasmic reticulum it transfers lipid from the membrane to the forming lipoprotein. Recent evidence suggests it may also function within the Golgi apparatus. To address this hypothesis we developed a polyclonal antibody to MTP and used it in a series of studies on mouse liver and McArdle RH7777 (McA) cells. Western blot analysis demonstrated the presence of MTP within mouse hepatic Golgi apparatus-rich fractions. In addition, in vitro lipid transfer assays demonstrated the presence of triglyceride transfer activity within the Golgi fractions. Immunohistochemical studies with mouse liver demonstrated the presence of MTP within all hepatocytes but not in nonparenchymal cells. The subcellular location of MTP in McA cells was investigated using confocal microscopy. MTP co-localized with TGN38 and GS28, markers for the trans- and cis-Golgi apparatus, respectively. Morphometric analyses indicated that approximately 17% of the MTP signal co-localized with the TGN38, while 33% of the trans-Golgi marker co-localized with the MTP. Approximately 17% of the MTP signal co-localized with the GS28, whereas 53% of the cis-Golgi marker co-localized with the MTP. The results provide unequivocal evidence for the location of MTP within the Golgi apparatus and further highlight the importance of this organelle in the assembly of lipoproteins.

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