Arf GTP-binding proteins and membrane traffic

Arf6 GTP结合蛋白已被证明调节膜运输和质膜上的细胞骨架。在包括乳腺癌在内的许多癌症模型系统中，已观察到Arf6及其调节因子上调。我们已经报道，质膜上活性Arf6的功能之一是招募Arno/细胞粘附素家族的鸟核苷酸交换因子，进而导致Arf1在细胞表面的激活(Cohen等人，2007)。这一发现表明，Arf蛋白在质膜上以顺序和级联的方式发挥作用。此外，Arf蛋白，如Arf1，以前被认为只在高尔基复合体发挥功能，这一发现促使我们研究Arf1可能在细胞表面发挥什么功能。我们发现Arf1在重排肌动蛋白细胞骨架以形成腹侧褶皱或足体样结构方面起着特定的作用。在Arf1水平被siRNA降低的细胞中，没有形成这些腹侧褶皱。这一发现使我们认为，许多归因于Arf6的膜交通和肌动蛋白细胞骨架的活性实际上可能涉及诸如Arf1等与高尔基体相关的ARF的角色。

The Arf6 GTP-binding protein has been shown to regulate both membrane traffic and the cytoskeleton at the plasma membrane. In a number of cancer model systems including breast cancer, Arf6 and its regulators have been observed to be upregulated. We have reported that one of the functions of active Arf6 at the plasma membrane is to recruit guanine nucleotide exchange factors of the ARNO/Cytohesin family that in turn lead to activation of Arf1 at the cell surface (Cohen et al 2007). This finding suggests that Arf proteins act sequentially and in a cascade at the plasma membrane. Furthermore, the finding that Arf proteins, such as Arf1, previously thought to only function at the Golgi complex, might function at the cell surface led us to investigate what functions Arf1 might serve there. We have found that Arf1 plays a specific role in rearranging the actin cytoskeleton to form ventral ruffles or podosome-like structures. Cells in which Arf1 levels were diminished by siRNA did not form these ventral ruffles. This finding leads us to suggest that many of the activites ascribed to Arf6 for both membrane traffic and the actin cytoskeleton might in fact involve roles for "Golgi-associated" Arfs such as Arf1.