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Two sphingolipid transfer proteins, CERT and FAPP2: Their roles in sphingolipid metabolism
Author(s) -
Yamaji Toshiyuki,
Kumagai Keigo,
Tomishige Nario,
Hanada Kentaro
Publication year - 2008
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.83
Subject(s) - pleckstrin homology domain , sphingolipid , golgi apparatus , microbiology and biotechnology , ceramide , endoplasmic reticulum , sphingomyelin , plant lipid transfer proteins , biochemistry , biology , kinase , serine , phosphorylation , chemistry , apoptosis , membrane , gene
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 PP2Cε 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. © 2008 IUBMB IUBMB Life, 60(8): 511–518, 2008