We continue to evaluate the roles played by Arf6 and also Golgi-associated Arfs like Arf1 at the plasma membrane. GTP-binding proteins like Arf cycle between GTP-bound, active and GDP-bound, inactive forms. Our finding that active forms of Arf6 can recruit Arf guanine nucleotide exchange factors or GEFs to membranes has formed the basis of a model whereby active Arf6 (Arf6-GTP) can recruit and activate other Arf proteins like Arf1, typically thought to function at the Golgi complex. We find that Arf1 is required for cortical actin rearrangements driven by activation of Src family kinases and protein kinase C. We are identifying which GEFs are involved in this process and also which GTPase activating proteins (GAPs) that turn off the Arf signal are involved.

Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2012
Total Cost
$251,889
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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
Grant, Barth D; Donaldson, Julie G (2009) Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 10:597-608
Scarselli, Marco; Donaldson, Julie G (2009) Constitutive internalization of G protein-coupled receptors and G proteins via clathrin-independent endocytosis. J Biol Chem 284:3577-85
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

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