Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry.
Protein kinase Gin4 negatively regulates flippase function and controls plasma membrane asymmetry.
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蛋白激酶 Gin4 负向调节翻转酶功能并控制质膜不对称。
DOI：
10.1083/jcb.201410076
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Thorner,Jeremy
中科院分区：
文献类型：
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作者：
Roelants,FrançoiseM;Su,BrookeM;vonWulffen,Joachim;Ramachandran,Subramaniam;Sartorel,Elodie;Trott,AmyE;Thorner,Jeremy
真核细胞质膜(PM)是一种复杂的结构，其中多种脂质物种以空间定义的方式排列在一起。PM脂在膜平面上横向排列成微域(Lingwood和Simons，2010)，也横向排列在膜上，因此双层的每个小叶都有不同的脂成分(Fadeel和Xue，2009)。小叶脂质含量的显著差异(称为双层不对称)首先在红细胞膜中被注意到(Gordesky和Marinetti，1973)，但在所有细胞类型中都是PM的特征(Devaux，1991；van Meer，2011)。胞外小叶富含磷脂酰胆碱、鞘磷脂和糖脂，而内叶富含磷脂酰乙醇胺(PtdEth)、磷脂酰丝氨酸(PtdSer)、磷脂酰肌醇(PtdIns)和衍生的磷脂酰肌醇(如PtdIns4，5P2；Devaux，1991；Fadeel和Xue，2009)。在PM生物发生过程中，双层不对称不会从头开始产生，但部分是由于PtdEth和PtdSer的主动向内移位(“翻转”)以及类似的外膜脂类向外移位(“flopping”；Daleke，2003；van Meer，2011)所产生的。面对持续的胞外囊泡插入和胞内囊泡去除所导致的PM重塑，维持双层不对称性是必要的，否则将扰乱小叶脂质含量。在真核生物中，PtdEth和PtdSer的内向易位是由P型ATPase的一个亚家族(4类)催化的，称为翻转酶(Daleke，2007；Lenoir等人，2007；Tanaka等人，2011；Sebastian等人，2012)。在发芽酵母中，有五种翻转酶：Dnf1、Dnf2、Dnf3、Drs2和Neo1(Catty等人，1997年)。Dnf1和Dnf2主要定位于PM，而Dnf3、Drs2和Neo1主要局限于细胞内膜(Daleke，2007)。Dnf1(1,571个残基)和Dnf2(1,612个残基)从内质网中退出以及它们在PM中的插入和功能需要它们与较小的
A eukaryotic plasma membrane (PM) is a complex structure in which a multitude of lipid species are arranged in a spatially defined manner. PM lipids are organized laterally in the plane of the membrane into microdomains (Lingwood and Simons, 2010) and also transversely across the membrane, such that each leaflet of the bilayer has a distinct lipid composition (Fadeel and Xue, 2009). The marked difference in leaflet lipid content (referred to as bilayer asymmetry) was first noted in the erythrocyte PM (Gordesky and Marinetti, 1973), but is characteristic of the PM in all cell types (Devaux, 1991; van Meer, 2011). The exocellular leaflet is enriched in phosphatidylcholine, sphingolipids, and glycolipids, whereas the inner leaflet is enriched in phosphatidylethanolamine (PtdEth), phosphatidylserine (PtdSer), phosphatidylinositol (PtdIns), and derived phosphoinositides (eg, PtdIns4, 5P2; Devaux, 1991; Fadeel and Xue, 2009). Bilayer asymmetry does not arise de novo during PM biogenesis, but is generated, in part, by active translocation of PtdEth and PtdSer inwards (“flipping”) along with similar translocation outwards of exoleaflet lipids (“flopping”; Daleke, 2003; van Meer, 2011). Maintenance of bilayer asymmetry is necessary in the face of the PM remodeling that results from continual exocytic vesicle insertion and endocytic vesicle removal, which would otherwise scramble leaflet lipid content. In eukaryotes, inward translocation of PtdEth and PtdSer is catalyzed by a subfamily (class 4) of P-type ATPases, dubbed flippases (Daleke, 2007; Lenoir et al., 2007; Tanaka et al., 2011; Sebastian et al., 2012). In budding yeast, there are five flippases: Dnf1, Dnf2, Dnf3, Drs2, and Neo1 (Catty et al., 1997). Dnf1 and Dnf2 localize primarily in the PM, whereas Dnf3, Drs2, and Neo1 are mainly confined to intracellular membranes (Daleke, 2007). Exit of Dnf1 (1,571 residues) and Dnf2 (1,612 residues) from the ER and their insertion and function in the PM requires their association with a smaller