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.
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