抄録
Synthesis and sorting of lipids are essential events for membrane biogenesis. However, the mechanisms underlying the transport of membrane lipids remain little understood. Ceramide is synthesized at the endoplasmic reticulum (ER), and translocated to the Golgi apparatus for conversion to sphingomyelin (SM). The main pathway of ER-to-Golgi trafficking of ceramide is genetically impaired in a CHO mutant cell line, LY-A [1-4]. After functional rescue experiments, we isolated a human cDNA that was able to fully complement LY-A cells, and named the 68-kDa protein encoded by the cDNA as CERT [5]. CERT is a cytoplasmic protein with a pleckstrin homology (PH) domain and a putative lipid transfer domain, START. The PH domain selectively binds phosphatidylinositol-4-monophosphate (PI4P), and can target the Golgi apparatus. The START can catalyse specific transfer of ceramide between membranes. CERT expressed in LY-A cells has an amino acid substitution that destroys its PI4P-binding activity, thereby impairing its Golgi-targeting function. Collectively, we conclude that CERT is central to ceramide-selective transport in the synthesis of SM, and propose the model that CERT extracts newly synthesized ceramide from the ER, and carries the ceramide molecule, in a non-vesicular manner, to the Golgi apparatus [5]. Refs. [1] Hanada et al., (1998) J. Biol. Chem., 273, 33787; [2] Fukasawa et al, (1999) J. Cell Biol., 144, 673; [3] Funakoshi et al, (2000) J. Biol. Chem., 275, 29938; [4] Yasuda et al, (2001) J. Biol. Chem., 276, 43994; [5] Hanada et al., (2003) Nature, 426, 803. [Jpn J Physiol 55 Suppl:S30 (2005)]
