Hanada Kentaro, Kumagai Keigo, Tomishige Nario, Yamaji Toshiyuki
Department of Biochemistry, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Biochim Biophys Acta. 2009 Jul;1791(7):684-91. doi: 10.1016/j.bbalip.2009.01.006. Epub 2009 Jan 22.
The transport and sorting of lipids from the sites of their synthesis to their appropriate destinations are fundamental for membrane biogenesis. In the synthesis of sphingolipids in mammalian cells, ceramide is newly produced at the endoplasmic reticulum (ER), and transported from the ER to the trans Golgi regions, where it is converted to sphingomyelin. CERT mediates the ER-to-Golgi trafficking of ceramide. CERT contains several functional domains and motifs including i) a START domain capable of catalyzing inter-membrane transfer of ceramide, ii) a pleckstrin homology domain, which serves to target the Golgi apparatus, iii) a FFAT motif which interacts with the ER-resident membrane protein VAP, and iv) a serine-repeat motif, of which hyperphosphorylation down-regulates CERT activity. It has been suggested that CERT extracts ceramide from the ER and carries it to the Golgi apparatus in a non-vesicular manner and that efficient CERT-mediated trafficking of ceramide occurs at membrane contact sites between the ER and the Golgi apparatus.
脂质从合成部位运输并分选到合适的目的地对于膜生物合成至关重要。在哺乳动物细胞中鞘脂的合成过程中，神经酰胺在内质网（ER）中新生合成，然后从内质网运输到反式高尔基体区域，在那里它被转化为鞘磷脂。CERT介导神经酰胺从内质网到高尔基体的运输。CERT包含几个功能域和基序，包括：i）一个能够催化神经酰胺膜间转移的START结构域；ii）一个用于靶向高尔基体的普列克底物蛋白同源结构域；iii）一个与内质网驻留膜蛋白VAP相互作用的FFAT基序；iv）一个丝氨酸重复基序，其过度磷酸化会下调CERT活性。有人提出，CERT以非囊泡方式从内质网提取神经酰胺并将其携带到高尔基体，并且高效的CERT介导的神经酰胺运输发生在内质网和高尔基体之间的膜接触部位。
