Choi J-Y, Riekhof W R, Wu W-I, Voelker D R
Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA.
Biochem Soc Trans. 2006 Jun;34(Pt 3):404-8. doi: 10.1042/BST0340404.
PtdSer (phosphatidylserine) is synthesized in the endoplasmic reticulum and the related MAM (mitochondria-associated membrane), and transported to the PtdSer decarboxylases, Pds1p in the mitochondria, and Psd2p in the Golgi. Genetic and biochemical analyses of PtdSer transport are now revealing the role of specific protein and lipid assemblies on different organelles that regulate non-vesicular PtdSer transport. The transport of PtdSer from MAM to mitochondria is regulated by at least three genes: MET30 (encoding a ubiquitin ligase), MET4 (encoding a transcription factor), and one or more unknown genes whose transcription is regulated by MET4. MET30-dependent ubiquitination is required for the MAM to function as a competent donor membrane and for the mitochondria to function as a competent acceptor membrane. Non-vesicular transport of PtdSer to the locus of Psd2p is under the control of at least three genes, STT4 [encoding Stt4p (phosphatidylinositol 4-kinase)], PSTB2 (encoding the lipid-binding protein PstB2p) and PSD2 (encoding Psd2p). Stt4p is proposed to produce a pool of PtdIns4P that is necessary for lipid transport. PstB2p and Psd2p must be present on the acceptor membrane for PtdSer transport to occur. Psd2p contains a C2 (Ca(2+) and phospholipid binding sequence) domain that is required for lipid transport. Reconstitution studies with chemically defined donor membranes demonstrate that membrane domains rich in the anionic lipids, PtdSer, PtdIns4P and phosphatidic acid function as the most efficient donors of PtdSer to Psd2p. The emerging view is that macromolecular complexes dependent on protein-protein and protein-lipid interactions form between donor and acceptor membranes and serve to dock the compartments and facilitate phospholipid transport.
磷脂酰丝氨酸（PtdSer）在内质网和相关的线粒体相关膜（MAM）中合成，并转运至线粒体中的PtdSer脱羧酶Pds1p以及高尔基体中的Psd2p。目前，对PtdSer转运的遗传学和生物化学分析揭示了不同细胞器上特定蛋白质和脂质组装体在调节非囊泡性PtdSer转运中的作用。PtdSer从MAM到线粒体的转运至少受三个基因调控：MET30（编码泛素连接酶）、MET4（编码转录因子），以及一个或多个转录受MET4调控的未知基因。MAM作为合适的供体膜发挥功能以及线粒体作为合适的受体膜发挥功能都需要MET30依赖性泛素化。PtdSer向Psd2p位点的非囊泡性转运受至少三个基因控制，即STT4[编码Stt4p（磷脂酰肌醇4激酶）]、PSTB2（编码脂质结合蛋白PstB2p）和PSD2（编码Psd2p）。有人提出Stt4p产生脂质转运所需的磷脂酰肌醇4磷酸（PtdIns4P）池。PtdSer转运发生时，PstB2p和Psd2p必须存在于受体膜上。Psd2p包含一个脂质转运所需的C2（钙离子和磷脂结合序列）结构域。用化学定义的供体膜进行的重组研究表明，富含阴离子脂质（PtdSer、PtdIns4P和磷脂酸）的膜结构域是向Psd2p转运PtdSer的最有效供体。新出现的观点是，依赖于蛋白质-蛋白质和蛋白质-脂质相互作用的大分子复合物在供体膜和受体膜之间形成，用于对接隔室并促进磷脂转运。
