Myriocin, an inhibitor of serine palmitoyl transferase, impairs the uptake of transferrin and low-density lipoprotein in mammalian cells |
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| Authors: | Sybille G E Meyer Agnieszka E Wendt Max Scherer Gerhard Liebisch Uta Kerkweg Gerd Schmitz Herbert de Groot |
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| Institution: | 1. Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany;2. Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Regensburg, Josef-Strauß-Allee 11, 93053 Regensburg, Germany;1. Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan;2. Laboratory of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan;3. Section of Inflammatory Bowel Disease & Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California 90095;4. College of Pharmacy, Pusan National University, Busan, 609-735, South Korea;1. Humboldt Universität zu Berlin, Institute for Chemistry, Berlin, Germany;2. Suez Canal University, Chemistry Department, Faculty of Science, Ismailia, Egypt;1. Institute of Protein Biochemistry, National Research Council of Italy, Naples, Italy;2. Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland |
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| Abstract: | The role of sphingolipids in clathrin-mediated endocytosis is only poorly understood in mammalian cells. Thus the relationship between sphingolipid de novo synthesis and clathrin-mediated endocytosis of transferrin were studied in L929 fibroblasts and two other cell lines. Endocytosis was measured using live cell imaging with fluorescent transferrin or (125)I-transferrin. Lipids were primarily measured using electrospray ionization tandem mass spectrometry. At physiological temperature, transferrin uptake was significantly decreased by the inhibitor of serine palmitoyl transferase myriocin. Myriocin inhibited also the uptake of low-density lipoproteins. The endocytosis inhibition by myriocin could be released by the addition of sphingoid base and by the protein phosphorylation effectors phorbol-12-myristate, 13-acetate (PMA) and okadaic acid. Myriocin influenced not only sphingolipids but also the glycerophospholipid profile. The study of phosphatidylcholine species shows adaptations to more saturated, alkylated and longer fatty acid moieties. The reported results imply that in mammalian cells, at 37°C, sphingolipid de novo synthesis is required for clathrin-mediated endocytosis. |
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