Arf GTP-binding proteins and membrane traffic

Arf 6 GTP结合蛋白已被证明可以调节质膜上的膜运输和细胞骨架。 在包括乳腺癌在内的许多癌症模型系统中，已经观察到Arf 6及其调节剂被上调。我们已经报道，质膜上活性Arf 6的功能之一是募集ARNO/细胞粘连蛋白家族的鸟嘌呤核苷酸交换因子，进而导致细胞表面Arf 1的活化（Cohen et al 2007）。 这一发现表明，Arf蛋白的作用顺序和级联在质膜。 此外，Arf蛋白，如Arf 1，以前被认为只在高尔基复合体中起作用，可能在细胞表面起作用，这一发现使我们研究Arf 1可能在那里起什么作用。 我们已经发现，Arf 1在重新排列肌动蛋白细胞骨架以形成腹侧皱褶或podosome样结构中起着特定的作用。 其中Arf 1水平被siRNA降低的细胞没有形成这些腹侧皱褶。 这一发现使我们认为，许多活动归因于Arf 6的膜交通和肌动蛋白细胞骨架可能实际上涉及的角色，如Arf 1的“高尔基体相关”Arfs。

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.