CdsA is involved in biosynthesis of glycolipid MPIase essential for membrane protein integration in vivo
CdsA is involved in biosynthesis of glycolipid MPIase essential for membrane protein integration in vivo
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DOI：
10.1038/s41598-018-37809-8
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发表时间：
2019-02-04
影响因子：
4.6
通讯作者：
Nishiyama, Ken-ichi
中科院分区：
文献类型：
--
作者：
Sawasato, Katsuhiro;Sato, Ryo;Nishiyama, Ken-ichi
MPIase 是一种参与膜蛋白整合的糖脂。尽管对其功能进行了体外评估，但缺乏 MPIase 生物合成信息阻碍了对其体内参与的验证。在这项研究中，我们发现CdsA（一种CDP-二酰基甘油合酶）的耗竭不仅会导致磷脂生物合成缺陷，还会导致MPIase耗竭，并导致膜蛋白M13外壳蛋白和分泌蛋白OmpA前体的积累。酵母 Tam41p 是一种线粒体 CDP-二酰基甘油合酶，可抑制磷脂生物合成的缺陷，但既不能恢复 MPIase 生物合成、前体加工，也不能恢复细胞生长，表明 MPIase 对于膜蛋白整合以及细胞生长至关重要。一致地，我们在体外观察到蛋白质整合到 MPIase 耗尽的膜囊泡中的严重缺陷。因此，MPIase 作为参与蛋白质整合的因子的功能在体内和体外都得到了证实。此外，Cds1p（一种真核生物 CdsA 同源物）显示出 MPIase 生物合成的潜力。根据这些结果，我们推测真核 MPIase 同源物的存在。
MPIase is a glycolipid that is involved in membrane protein integration. Despite evaluation of its functions in vitro, the lack of information on MPIase biosynthesis hampered verification of its involvement in vivo. In this study, we found that depletion of CdsA, a CDP-diacylglycerol synthase, caused not only a defect in phospholipid biosynthesis but also MPIase depletion with accumulation of the precursors of both membrane protein M13 coat protein and secretory protein OmpA. Yeast Tam41p, a mitochondrial CDP-diacylglycerol synthase, suppressed the defect in phospholipid biosynthesis, but restored neither MPIase biosynthesis, precursor processing, nor cell growth, indicating that MPIase is essential for membrane protein integration and therefore for cell growth. Consistently, we observed a severe defect in protein integration into MPIase-depleted membrane vesicles in vitro. Thus, the function of MPIase as a factor involved in protein integration was proven in vivo as well as in vitro. Moreover, Cds1p, a eukaryotic CdsA homologue, showed a potential for MPIase biosynthesis. From these results, we speculate the presence of a eukaryotic MPIase homologue.