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首页> 外文期刊>Molecular and Cellular Biology >H-Ras Distribution and Signaling in Plasma Membrane Microdomains Are Regulated by Acylation and Deacylation Events
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H-Ras Distribution and Signaling in Plasma Membrane Microdomains Are Regulated by Acylation and Deacylation Events

机译：血浆膜微区的H-Ras分布和信号传导受酰化和脱酰事件的调节

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H-Ras must adhere to the plasma membrane to be functional. This is accomplished by posttranslational modifications, including palmitoylation, a reversible process whereby H-Ras traffics between the plasma membrane and the Golgi complex. At the plasma membrane, H-Ras has been proposed to occupy distinct sublocations, depending on its activation status: lipid rafts/detergent-resistant membrane fractions when bound to GDP, diffusing to disordered membrane/soluble fractions in response to GTP loading. Herein, we demonstrate that H-Ras sublocalization is dictated by its degree of palmitoylation in a cell type-specific manner. Whereas H-Ras localizes to detergent-resistant membrane fractions in cells with low palmitoylation activity, it locates to soluble membrane fractions in lineages where it is highly palmitoylated. Interestingly, in both cases GTP loading results in H-Ras diffusing away from its original sublocalization. Moreover, tilting the equilibrium between palmitoylation and depalmitoylation processes can substantially alter H-Ras segregation and, subsequently, its biochemical and biological functions. Thus, the palmitoylation/depalmitoylation balance not only regulates H-Ras cycling between endomembranes and the plasma membrane but also serves as a key orchestrator of H-Ras lateral diffusion between different types of plasma membrane and thereby of H-Ras signaling.
机译：H-Ras必须粘附在质膜上才能起作用。这是通过翻译后修饰来实现的，包括棕榈酰化，这是一种可逆的过程，在此过程中H-Ras在质膜和高尔基体之间运输。在质膜上，已提出H-Ras取决于其活化状态，占据不同的亚位：当与GDP结合时，脂筏/抗洗涤剂的膜级分会响应GTP负载而扩散到无序的膜/可溶性级分。在本文中，我们证明H-Ras的亚定位是由其棕榈酰化程度以细胞类型特异性方式决定的。尽管H-Ras定位于棕榈酰化活性低的细胞中耐去污剂的膜部分，但它位于高度棕榈酰化的谱系中的可溶性膜部分。有趣的是，在两种情况下，GTP加载都会导致H-Ras从其原始的亚定位扩散开来。此外，倾斜棕榈酰化和去棕榈酸酯化过程之间的平衡可以显着改变H-Ras分离，进而改变其生化和生物学功能。因此，棕榈酰化/去棕榈酰化的平衡不仅调节内膜和质膜之间的H-Ras循环，而且还充当不同类型的质膜之间的H-Ras横向扩散并由此引起H-Ras信号传导的关键协调器。

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