Zachowski A, Henry J P, Devaux P F
Institut de Biologie Physico-Chimique, Paris, France.
Nature. 1989 Jul 6;340(6228):75-6. doi: 10.1038/340075a0.
The Ca2+-dependent binding of annexin proteins to secretory granule membranes seems to be involved in the early stage of exocytosis. Binding studies have shown that these proteins have a specificity for phosphatidylserine (PtdS) interfaces. Furthermore, aminolipids are necessary for contact and fusion between lipid vesicles or between liposomes and chromaffin granules. Thus, PtdS must be present on the granule outer (cytoplasmic) monolayer. We report here that chromaffin granules possess a mechanism to maintain PtdS orientation, comparable to the ATP-dependent aminophospholipid translocase from human erythrocytes. The translocase, in granules, selectively transports PtdS from the luminal to the cytoplasmic monolayer, provided the incubation medium contains ATP. As this protein shares several properties with the granule vanadate-sensitive ATPase II, we infer that this ATPase, of relative molecular mass 115,000, is the protein responsible for aminophospholipid translocation. This is the first evidence for an ATP-dependent specific phospholipid 'flippase' in intracellular organelles.
膜联蛋白与分泌颗粒膜的钙离子依赖性结合似乎参与了胞吐作用的早期阶段。结合研究表明，这些蛋白质对磷脂酰丝氨酸（PtdS）界面具有特异性。此外，氨基脂质对于脂质囊泡之间或脂质体与嗜铬颗粒之间的接触和融合是必需的。因此，PtdS必须存在于颗粒的外（细胞质）单层中。我们在此报告，嗜铬颗粒具有一种维持PtdS取向的机制，类似于人红细胞中依赖ATP的氨基磷脂转位酶。颗粒中的转位酶在孵育介质含有ATP的情况下，选择性地将PtdS从腔单层转运到细胞质单层。由于该蛋白质与颗粒钒酸盐敏感的ATP酶II具有几个共同特性，我们推断相对分子质量为115,000的这种ATP酶是负责氨基磷脂转位的蛋白质。这是细胞内细胞器中存在依赖ATP的特异性磷脂“翻转酶”的首个证据。
