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.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2010
Total Cost
$306,619
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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Donaldson, Julie G; Johnson, Debra L; Dutta, Dipannita (2016) Rab and Arf G Proteins in Endosomal Trafficking & Cell Surface Homeostasis. Small GTPases :0
Dutta, Dipannita; Donaldson, Julie G (2015) Rab and Arf G proteins in endosomal trafficking. Methods Cell Biol 130:127-38
Caviston, Juliane P; Cohen, Lee Ann; Donaldson, Julie G (2014) Arf1 and Arf6 promote ventral actin structures formed by acute activation of protein kinase C and Src. Cytoskeleton (Hoboken) 71:380-94
Donaldson, Julie G; Jackson, Catherine L (2011) ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol 12:362-75
Sakurai, Atsuko; Jian, Xiaoying; Lee, Charity J et al. (2011) Phosphatidylinositol-4-phosphate 5-kinase and GEP100/Brag2 protein mediate antiangiogenic signaling by semaphorin 3E-plexin-D1 through Arf6 protein. J Biol Chem 286:34335-45
Cohen, Lee Ann; Donaldson, Julie G (2010) Analysis of Arf GTP-binding protein function in cells. Curr Protoc Cell Biol Chapter 3:Unit 14.12.1-17
Donaldson, Julie G; Williams, David B (2009) Intracellular assembly and trafficking of MHC class I molecules. Traffic 10:1745-52
Eyster, Craig A; Higginson, Jason D; Huebner, Robert et al. (2009) Discovery of new cargo proteins that enter cells through clathrin-independent endocytosis. Traffic 10:590-9
Donaldson, Julie G (2009) Phospholipase D in endocytosis and endosomal recycling pathways. Biochim Biophys Acta 1791:845-9
Donaldson, Julie G; McPherson, Peter S (2009) Membrane trafficking heats up in Pavia. Golgi Meeting on Membrane Trafficking in Global Cellular Responses. EMBO Rep 10:132-6

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