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. We have found that Arf1, typically thought to function at the Golgi complex, is required for ventral actin structures formed in response to phorbol ester treatment. Phorbol esters like PMA are tumor promoters and lead to the activation of protein kinase C and Src family kinases. These ventral actin structures represent a major re-organization of the cortical actin cytoskeleton and focal adhesions. This adds to the growing list of cellular activities occurring at the plasma membrane that now are thought to involve Arf1. All Arf protein share common effectors (stimulation of phospholipase D, and phosphatidylinositol 4-phosphate 5-kinase) however they may be activated by different guanine nucleotide exchange factors (GEFs) and GTP-ase activating proteins (GAPs). Furthermore these GEFs and GAPs themselves may have unique signaling and scaffolding functions giving rise to distinct signaling outputs.

Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2013
Total Cost
$136,468
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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
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
Grant, Barth D; Donaldson, Julie G (2009) Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 10:597-608
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
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 (2009) Phospholipase D in endocytosis and endosomal recycling pathways. Biochim Biophys Acta 1791:845-9
Jacobs, Damon T; Weigert, Roberto; Grode, Kyle D et al. (2009) Myosin Vc is a molecular motor that functions in secretory granule trafficking. Mol Biol Cell 20:4471-88
Donaldson, Julie G (2008) Arfs and membrane lipids: sensing, generating and responding to membrane curvature. Biochem J 414:e1-2