Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi trafficking of ceramide

Synthesis and sorting of lipids are essential events for membrane biogenesis and its homeostasis. Ceramide is synthesised at the endoplasmic reticulum (ER), and translocated to the Golgi compartment for conversion to sphingomyelin (SM). We have recently identified a key factor (named CERT) for ceramide trafficking. In this short review, I summarise recent advances in molecular mechanisms of intracellular transport of ceramide, focusing on our genetic and biochemical approaches to this issue.

[1]  M. Umeda,et al.  Lysenin, a Novel Sphingomyelin-specific Binding Protein* , 1998, The Journal of Biological Chemistry.

[2]  S. Yasuda,et al.  CERT Mediates Intermembrane Transfer of Various Molecular Species of Ceramides* , 2005, Journal of Biological Chemistry.

[3]  D. S. Keller,et al.  Semi-intact cells permeable to macromolecules: Use in reconstitution of protein transport from the endoplasmic reticulum to the Golgi complex , 1987, Cell.

[4]  S. Munro.  Cell biology: Earthworms and lipid couriers , 2003, Nature.

[5]  Brad J Marsh,et al.  Predicting Function from Structure: 3D Structure Studies of the Mammalian Golgi Complex , 2004, Traffic.

[6]  H. Riezman,et al.  Lipid pickup and delivery , 2004, Nature Cell Biology.

[7]  M. Roth,et al.  Phosphatidylinositol 4 Phosphate Regulates Targeting of Clathrin Adaptor AP-1 Complexes to the Golgi , 2003, Cell.

[8]  D. Schmitt,et al.  The mitochondria-associated endoplasmic-reticulum subcompartment (MAM fraction) of rat liver contains highly active sphingolipid-specific glycosyltransferases. , 2003, The Biochemical journal.

[9]  K. Hanada,et al.  Mammalian Cell Mutants Resistant to a Sphingomyelin-directed Cytolysin , 1998, The Journal of Biological Chemistry.

[10]  C. Simon,et al.  Exchange of C(16)-ceramide between phospholipid vesicles. , 1999, Biochemistry.

[11]  F. Wieland,et al.  Glucosylceramide is synthesized at the cytosolic surface of various Golgi subfractions , 1992, The Journal of cell biology.

[12]  K. Sandhoff,et al.  Biosynthesis and degradation of mammalian glycosphingolipids. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[13]  K. Sandhoff,et al.  Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver. , 1992, The Journal of biological chemistry.

[14]  J. Forteza,et al.  Goodpasture Antigen-binding Protein, the Kinase That Phosphorylates the Goodpasture Antigen, Is an Alternatively Spliced Variant Implicated in Autoimmune Pathogenesis* , 2000, The Journal of Biological Chemistry.

[15]  A. Herrmann,et al.  Protein-mediated transbilayer movement of lipids in eukaryotes and prokaryotes: the relevance of ABC transporters. , 2003, International journal of antimicrobial agents.

[16]  R. Pagano,et al.  Determination of the intracellular sites and topology of glucosylceramide synthesis in rat liver. , 1991, The Biochemical journal.

[17]  Alfred H. Merrill,et al.  De Novo Sphingolipid Biosynthesis: A Necessary, but Dangerous, Pathway* , 2002, The Journal of Biological Chemistry.

[18]  D. Welker.  Lipid assembly into cell membranes , 2002 .

[19]  G. van Meer,et al.  Sphingolipid transport in eukaryotic cells. , 2000, Biochimica et biophysica acta.

[20]  J. Breslow,et al.  Intracellular Cholesterol Transport , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[21]  J. Slotte,et al.  Cholesterol interactions with phospholipids in membranes. , 2002, Progress in lipid research.

[22]  C. Ponting,et al.  START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins. , 1999, Trends in biochemical sciences.

[23]  J. Brouwers,et al.  Identification of a family of animal sphingomyelin synthases , 2004, The EMBO journal.

[24]  C. Deng,et al.  [A vital role for glycosphingolipid synthesis during development and differentiation]. , 1999, Seikagaku. The Journal of Japanese Biochemical Society.

[25]  R. Ueda,et al.  Drosophila Glucosylceramide Synthase , 2004, Journal of Biological Chemistry.

[26]  D. Kabat,et al.  Exceptional fusogenicity of Chinese hamster ovary cells with murine retroviruses suggests roles for cellular factor(s) and receptor clusters in the membrane fusion process , 1996, Journal of virology.

[27]  F. Revert,et al.  Characterization of a Novel Type of Serine/Threonine Kinase That Specifically Phosphorylates the Human Goodpasture Antigen* , 1999, The Journal of Biological Chemistry.

[28]  Shohei Yamaoka,et al.  Expression Cloning of a Human cDNA Restoring Sphingomyelin Synthesis and Cell Growth in Sphingomyelin Synthase-defective Lymphoid Cells* , 2004, Journal of Biological Chemistry.

[29]  S. Dowler,et al.  Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities. , 2000, The Biochemical journal.

[30]  Christopher J. R. Loewen,et al.  A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP , 2003, The EMBO journal.

[31]  A. Merrill,et al.  Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. , 1991, The Journal of biological chemistry.

[32]  Satoshi Yasuda,et al.  Molecular machinery for non-vesicular trafficking of ceramide , 2003, Nature.

[33]  J. Rothman,et al.  Sar1 promotes vesicle budding from the endoplasmic reticulum but not Golgi compartments , 1994, The Journal of cell biology.

[34]  T. Kitamura,et al.  Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. , 2003, Experimental hematology.

[35]  S. Munro,et al.  Targeting of Golgi-Specific Pleckstrin Homology Domains Involves Both PtdIns 4-Kinase-Dependent and -Independent Components , 2002, Current Biology.

[36]  L. Liscum,et al.  Intracellular cholesterol transport. , 1992, Journal of lipid research.

[37]  R. Schekman,et al.  Bi-directional protein transport between the ER and Golgi. , 2004, Annual review of cell and developmental biology.

[38]  K. Hanada,et al.  Reconstitution of ATP- and Cytosol-dependent Transport of de Novo Synthesized Ceramide to the Site of Sphingomyelin Synthesis in Semi-intact Cells* , 2000, The Journal of Biological Chemistry.

[39]  K. Hanada,et al.  Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. , 2003, Biochimica et biophysica acta.

[40]  K. Hanada,et al.  Reduction of Sphingomyelin Level without Accumulation of Ceramide in Chinese Hamster Ovary Cells Affects Detergent-resistant Membrane Domains and Enhances Cellular Cholesterol Efflux to Methyl-β-cyclodextrin* , 2000, The Journal of Biological Chemistry.

[41]  D. Vance,et al.  Biochemistry of Lipids, Lipoproteins and Membranes , 2002 .

[42]  D. Stephens,et al.  Biogenesis of ER-to-Golgi transport carriers: complex roles of COPII in ER export. , 2004, Trends in cell biology.

[43]  Y. Hirabayashi,et al.  Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[44]  K. Locher,et al.  ABC transporter architecture and mechanism: implications from the crystal structures of BtuCD and BtuF , 2004, FEBS letters.

[45]  K. Hanada,et al.  Genetic Evidence for ATP-dependent Endoplasmic Reticulum-to-Golgi Apparatus Trafficking of Ceramide for Sphingomyelin Synthesis in Chinese Hamster Ovary Cells , 1999, The Journal of cell biology.

[46]  Y. Hannun,et al.  Lipid Metabolism: Ceramide Transfer Protein Adds a New Dimension , 2004, Current Biology.

[47]  J. Breslow,et al.  StAR-related Lipid Transfer (START) Proteins: Mediators of Intracellular Lipid Metabolism* , 2003, Journal of Biological Chemistry.

[48]  B. Stieger,et al.  Sphingomyelin synthesis in rat liver occurs predominantly at the cis and medial cisternae of the Golgi apparatus. , 1990, The Journal of biological chemistry.