Sphingolipid metabolism and interorganellar transport: localization of sphingolipid enzymes and lipid transfer proteins.
In recent decades, many sphingolipid enzymes, sphingolipid-metabolism regulators and sphingolipid transfer proteins have been isolated and characterized. This review will provide an overview of the intracellular localization and topology of sphingolipid enzymes in mammalian cells to highlight the locations where respective sphingolipid species are produced. Interestingly, three sphingolipids that reside or are synthesized in cytosolic leaflets of membranes (ceramide, glucosylceramide and ceramide-1-phosphate) all have cytosolic lipid transfer proteins (LTPs). These LTPs consist of ceramide transfer protein (CERT), four-phosphate adaptor protein 2 (FAPP2) and ceramide-1-phosphate transfer protein (CPTP), respectively. These LTPs execute functions that affect both the location and metabolism of the lipids they bind. Molecular details describing the mechanisms of regulation of LTPs continue to emerge and reveal a number of critical processes, including competing phosphorylation and dephosphorylation reactions and binding interactions with regulatory proteins and lipids that influence the transport, organelle distribution and metabolism of sphingolipids.
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
Toshiyuki
T
Yamaji
Kentaro
K
Hanada
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D021381:Protein Transport; D013107:Sphingolipids / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D049294:Phospholipid Transfer Proteins; D013107:Sphingolipids
CERT; glycolipid; lipid transfer protein; membrane contact site; metabolism; sphingolipid