Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9886554 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2005 | 15 Pages |
Abstract
De novo biosynthesis of sphingolipids begins in the endoplasmic reticulum (ER) and continues in the Golgi apparatus and plasma membrane. A crucial step in sphingolipid biosynthesis is the transport of ceramide by vesicular and non-vesicular mechanisms from its site of synthesis in the ER to the Golgi apparatus. The recent discovery of the ceramide transport protein CERT has revealed a novel pathway for the delivery of ceramide to the Golgi apparatus for sphingomyelin (SM) synthesis. In addition to a ceramide-binding START domain, CERT has FFAT (referring to two phenylalanines [FF] in an acidic tract) and pleckstrin homology (PH) domains that recognize the ER integral membrane protein VAMP-associated protein (VAP) and Golgi-associated PtdIns 4-phosphate, respectively. Mechanisms for vectorial transport involving dual-organellar targeting and sites of deposition of ceramide in the Golgi apparatus are proposed. Similar Golgi-ER targeting motifs are also present in the oxysterol-binding protein (OSBP), which regulates ceramide transport and SM synthesis in an oxysterol-dependent manner. Consequently, this emerges as a potential mechanism for integration of sphingolipid and cholesterol metabolism. The identification of organellar targeting motifs in other related lipid-binding/transport proteins indicate that concepts learned from the study of ceramide transport can be applied to other lipid transport processes.
Keywords
PtdChoGPiVAPARFTGNSREBPCERTGlcCerKDSPtdIns25-OHOSBPFFATVesicle-associated membrane protein-associated proteinFAPPSTARD4D609OSBP-related proteinPITPPCTPinositol phosphorylceramideIPCORPGFPMCsERKSPT25-Hydroxycholesterolsphingomyelinsphingomyelin synthasephosphatidic acidChoLagChinese Hamster OvaryLipid transportGolgi apparatusdiacylglycerolDAGMembrane contact sitesStarceramideceramide glucosyltransferaseTrans-Golgi networkendoplasmic reticulumstartPlasma membraneADP-ribosylation factorphosphatidylinositolphosphatidylcholinePleckstrin HomologyhydroxycholesterolOxysterol-binding proteinphosphatidylcholine transfer proteinphosphatidylinositol transfer proteinSteroidogenic acute regulatory proteinceramide transport proteingreen fluorescent proteinSerine palmitoyltransferaseSMSextracellular signal-regulated kinaseglucosylceramideglycosylphosphatidylinositol
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Authors
Ryan J. Perry, Neale D. Ridgway,