title: Two sphingolipid transfer proteins, CERT and FAPP2: their roles in sphingolipid metabolism.
abstract: Recent discoveries of two sphingolipid transfer proteins, CERT and FAPP2, have brought the field of sphingolipid metabolism to a more dynamic stage. CERT transfers ceramide from the endoplasmic reticulum (ER) to the Golgi apparatus, a step crucial for sphingomyelin (SM) synthesis. The pleckstrin homology (PH) domain and the FFAT motif of CERT restrict the direction of transfer and destination of ceramide through binding to phosphatidylinositol 4-monophosphate (PI4P) at the Golgi and the ER resident proteins, VAPs, respectively. CERT is regulated by the phosphorylation and dephosphorylation of serine/threonine, in which protein kinase D, possibly casein kinase I, and PP2Cepsilon are involved. On the other hand, FAPP2 transfers glucosylceramide (GlcCer) to appropriate sites for the synthesis of complex glycosphingolipids. Like CERT, FAPP2 contains a PH domain, the binding of which to PI4P is required for its localization to the Golgi. These observations indicate that lipid transfer proteins, CERT and FAPP2, spatially regulate lipid metabolism on the cytosolic side.
authors.affiliation: Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamaji
authors.forename: Keigo
authors.initials: K
authors.lastname: Kumagai
authors.forename: Nario
authors.initials: N
authors.lastname: Tomishige
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hanada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002518:Ceramides / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002518:Ceramides; C487038:PLEKHA8 protein, human; D013107:Sphingolipids; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases