adp ribosylation factors


Summary: MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC

Top Publications

  1. Pajcini K, Pomerantz J, Alkan O, Doyonnas R, Blau H. Myoblasts and macrophages share molecular components that contribute to cell-cell fusion. J Cell Biol. 2008;180:1005-19 pubmed publisher
    ..Our results are the first to demonstrate a role for a single protein in the fusion of two different cell types, and provide novel mechanistic insight into the function of GEFs in the morphological maturation of multinucleated cells. ..
  2. Tsai P, Lee S, Liu Y, Chu C, Chen K, Ho J, et al. Afi1p functions as an Arf3p polarization-specific docking factor for development of polarity. J Biol Chem. 2008;283:16915-27 pubmed publisher
    ..Our findings demonstrate that Afi1p functions as an Arf3p polarization-specific adapter and participates in development of polarity. ..
  3. Robertson S, Setty S, Sitaram A, Marks M, Lewis R, Chou M. Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking. Mol Biol Cell. 2006;17:645-57 pubmed
    ..These studies reveal a previously unappreciated link of Erk signaling to organelle dynamics and endosomal trafficking. ..
  4. Esteban P, Yoon H, Becker J, Dorsey S, Caprari P, Palko M, et al. A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin. J Cell Biol. 2006;173:291-9 pubmed
    ..Thus, our data identify a new signaling pathway elicited by the kinase-deficient TrkCT1 receptor. Moreover, we establish NT3 as an upstream regulator of Arf6. ..
  5. Schrick J, Vogel P, Abuin A, Hampton B, Rice D. ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor development. Am J Pathol. 2006;168:1288-98 pubmed
    ..Moreover, mice lacking Arl3 exhibited photoreceptor degeneration as early as postnatal day 14. These results are the first to implicate Arl3 in a ciliary disease affecting the kidney, biliary tract, pancreas, and retina. ..
  6. Honda A, Al Awar O, Hay J, Donaldson J. Targeting of Arf-1 to the early Golgi by membrin, an ER-Golgi SNARE. J Cell Biol. 2005;168:1039-51 pubmed
    ..These studies suggest that membrin recruits Arf-1 to the early Golgi and reveal distinct kinetic cycles for Arf-1 at early and late Golgi determined by different sets of Arf regulators and effectors. ..
  7. Frigerio G, Grimsey N, Dale M, Majoul I, Duden R. Two human ARFGAPs associated with COP-I-coated vesicles. Traffic. 2007;8:1644-55 pubmed
    ..However, silencing all three ARFGAPs causes cell death. Our data provide strong evidence that ARFGAP2 and ARFGAP3 function in COP I traffic. ..
  8. Hall B, McLean M, Davis K, Casanova J, Sligar S, Schwartz M. A fluorescence resonance energy transfer activation sensor for Arf6. Anal Biochem. 2008;374:243-9 pubmed
    ..The addition of platelet-derived growth factor (PDGF) to fibroblasts triggered a rapid and transient increase in FRET, indicative of Arf6 activation. These reagents should be useful for investigations of Arf6 activation and function. ..
  9. Gong Q, Weide M, Huntsman C, Xu Z, Jan L, Ma D. Identification and characterization of a new class of trafficking motifs for controlling clathrin-independent internalization and recycling. J Biol Chem. 2007;282:13087-97 pubmed
    ..Moreover our data suggest that these motifs may enhance the association of membrane proteins with the EFA6 family of guanine nucleotide exchange factors for ADP-ribosylation factor 6. ..

More Information


  1. Bigay J, Casella J, Drin G, Mesmin B, Antonny B. ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif. EMBO J. 2005;24:2244-53 pubmed
    ..This helix differs from classical amphipathic helices by the abundance of serine and threonine residues on its polar face. ..
  2. Donaldson J, Honda A. Localization and function of Arf family GTPases. Biochem Soc Trans. 2005;33:639-42 pubmed
    ..Whereas Arf6 is targeted to the plasma membrane through multiple regions along the protein, we have found a Golgi-targeting region in Arf1 that is sufficient to target Arf6 to the Golgi complex. ..
  3. Anders N, Jurgens G. Large ARF guanine nucleotide exchange factors in membrane trafficking. Cell Mol Life Sci. 2008;65:3433-45 pubmed publisher
    ..Furthermore we highlight common themes and apparent differences in large ARF-GEF function between eukaryotic kingdoms. ..
  4. Hu B, Shi B, Jarzynka M, Yiin J, D SOUZA SCHOREY C, Cheng S. ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain GTPase-activating protein 1-Rac1-mediated pathway. Cancer Res. 2009;69:794-801 pubmed publisher
    ..Taken together, these data suggest that ARF6-mediated Rac1 activation is essential for glioma cell invasion via a signaling pathway that requires IQGAP1. ..
  5. Hafner M, Schmitz A, Grüne I, Srivatsan S, Paul B, Kolanus W, et al. Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance. Nature. 2006;444:941-4 pubmed
    ..Because insulin resistance is among the earliest pathological changes in type 2 diabetes, our results show the potential of chemical biology for dissecting the molecular pathogenesis of this disease. ..
  6. Prag G, Lee S, Mattera R, Arighi C, Beach B, Bonifacino J, et al. Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding proteins. Proc Natl Acad Sci U S A. 2005;102:2334-9 pubmed
    ..This ability highlights the GAT domain as a hub for interactions with multiple partners in trafficking. ..
  7. Cotton M, Boulay P, Houndolo T, Vitale N, Pitcher J, Claing A. Endogenous ARF6 interacts with Rac1 upon angiotensin II stimulation to regulate membrane ruffling and cell migration. Mol Biol Cell. 2007;18:501-11 pubmed
    ..Taken together, our findings reveal a novel function of endogenously expressed ARF6 and demonstrate that by interacting with Rac1, this small GTPase is a central regulator of the signaling pathways leading to actin remodeling. ..
  8. Yano H, Kobayashi I, Onodera Y, Luton F, Franco M, Mazaki Y, et al. Fbx8 makes Arf6 refractory to function via ubiquitination. Mol Biol Cell. 2008;19:822-32 pubmed
    ..Our results indicate that dysfunction of Fbx8 expression may contribute to the invasiveness of some breast cancer cells. ..
  9. Casanova J. Regulation of Arf activation: the Sec7 family of guanine nucleotide exchange factors. Traffic. 2007;8:1476-85 pubmed
    The ADP ribosylation factors (Arfs) are a family of small, ubiquitously expressed and evolutionarily conserved guanosine triphosphatases that are key regulators of vesicular transport in eukaryotic cells (D'Souza-Schorey C, Chavrier P...
  10. Liu W, Duden R, Phair R, Lippincott Schwartz J. ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells. J Cell Biol. 2005;168:1053-63 pubmed
    ..These data suggest that ArfGAP1, coatomer and Arf1 play interdependent roles in the assembly-disassembly cycle of the COPI coat in vivo. ..
  11. Morishige M, Hashimoto S, Ogawa E, Toda Y, Kotani H, Hirose M, et al. GEP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion. Nat Cell Biol. 2008;10:85-92 pubmed
    ..Our results indicate that GEP100 links EGFR signalling to Arf6 activation to induce invasive activities of some breast cancer cells, and hence may contribute to their metastasis and malignancy. ..
  12. Zhou C, Cunningham L, Marcus A, Li Y, Kahn R. Arl2 and Arl3 regulate different microtubule-dependent processes. Mol Biol Cell. 2006;17:2476-87 pubmed
    ..We conclude that Arl2 and Arl3 have related but distinct roles at centrosomes and in regulating microtubule-dependent processes. ..
  13. Inoue H, Randazzo P. Arf GAPs and their interacting proteins. Traffic. 2007;8:1465-75 pubmed
    ..Here we describe the Arf GAP family and summarize the currently identified protein interactors in the context of known Arf GAP functions. ..
  14. Choi W, Karim Z, Whiteheart S. Arf6 plays an early role in platelet activation by collagen and convulxin. Blood. 2006;107:3145-52 pubmed
    ..These data show that Arf6 is a key element in activation through GPVI, and is required for activation of the Rho family GTPases and the subsequent cytoskeletal rearrangements needed for full platelet function. ..
  15. Randazzo P, Inoue H, Bharti S. Arf GAPs as regulators of the actin cytoskeleton. Biol Cell. 2007;99:583-600 pubmed
    ..With multiple functional elements, the Arf GAPs could integrate signals and biochemical activities that result in co-ordinated changes in actin and membranes necessary for a wide range of cellular functions. ..
  16. Beemiller P, Hoppe A, Swanson J. A phosphatidylinositol-3-kinase-dependent signal transition regulates ARF1 and ARF6 during Fcgamma receptor-mediated phagocytosis. PLoS Biol. 2006;4:e162 pubmed
    ..This indicates that a PI-3K-dependent signal transition defines the sequence of ARF GTPase activation during phagocytosis and that ARF6 and ARF1 coordinate different functions at the forming phagosome. ..
  17. Hofmann I, Thompson A, Sanderson C, Munro S. The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane. Curr Biol. 2007;17:711-6 pubmed
    ..The Arl4 family thus defines a signal-transduction pathway that can mediate the plasma-membrane recruitment of cytohesins independently of a requirement for the generation of PtdIns(3,4,5)P(3). ..
  18. Mazelova J, Astuto Gribble L, Inoue H, Tam B, Schonteich E, Prekeris R, et al. Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4. EMBO J. 2009;28:183-92 pubmed publisher
    ..As the VxPx motif is present in other ciliary membrane proteins, the Arf4-based targeting complex is most likely a part of conserved machinery involved in the selection and packaging of the cargo destined for delivery to the cilium. ..
  19. Veltel S, Gasper R, Eisenacher E, Wittinghofer A. The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3. Nat Struct Mol Biol. 2008;15:373-80 pubmed publisher
    ..The cognate G protein-GAP pair is conserved in yeast as Cin4-Cin2, and the ability of RP2 to act as a GAP can be correlated with its ability to complement a CIN2-deletion phenotype. ..
  20. Volpicelli Daley L, Li Y, Zhang C, Kahn R. Isoform-selective effects of the depletion of ADP-ribosylation factors 1-5 on membrane traffic. Mol Biol Cell. 2005;16:4495-508 pubmed
  21. Ha V, Thomas G, Stauffer S, Randazzo P. Preparation of myristoylated Arf1 and Arf6. Methods Enzymol. 2005;404:164-74 pubmed
    ..Here, we describe methods that yield homogeneous preparations of myristoylated Arf1 and Arf6. ..
  22. Paleotti O, Macia E, Luton F, Klein S, Partisani M, Chardin P, et al. The small G-protein Arf6GTP recruits the AP-2 adaptor complex to membranes. J Biol Chem. 2005;280:21661-6 pubmed
    ..These findings strongly suggest that Arf6 plays a major role in clathrin-mediated endocytosis by directly controlling the assembly of the AP-2/clathrin coat. ..
  23. Muralidharan Chari V, Hoover H, Clancy J, Schweitzer J, Suckow M, Schroeder V, et al. ADP-ribosylation factor 6 regulates tumorigenic and invasive properties in vivo. Cancer Res. 2009;69:2201-9 pubmed publisher
    ..These findings document an intricate role for ARF6 and the regulation of ERK activation in orchestrating mechanisms underlying melanoma growth, invasion, and metastases. ..
  24. Lay D, L Grosshans B, Heid H, Gorgas K, Just W. Binding and functions of ADP-ribosylation factor on mammalian and yeast peroxisomes. J Biol Chem. 2005;280:34489-99 pubmed
    ..ScARF1 regulated this process in a positive manner, and ScARF3 regulated it in a negative manner. ..
  25. Hattula K, Furuhjelm J, Tikkanen J, Tanhuanpää K, Laakkonen P, Peranen J. Characterization of the Rab8-specific membrane traffic route linked to protrusion formation. J Cell Sci. 2006;119:4866-77 pubmed
    ..We propose that Rab8 regulates a membrane-recycling pathway that mediates protrusion formation. ..
  26. Donaldson J. Arfs and membrane lipids: sensing, generating and responding to membrane curvature. Biochem J. 2008;414:e1-2 pubmed publisher
    ..These findings suggest that Arf protein activation and membrane interaction may initiate membrane curvature that will be enhanced further by coat proteins during vesicle formation. ..
  27. Zhao X, Claude A, Chun J, Shields D, Presley J, Melancon P. GBF1, a cis-Golgi and VTCs-localized ARF-GEF, is implicated in ER-to-Golgi protein traffic. J Cell Sci. 2006;119:3743-53 pubmed
    ..Strikingly, microinjection of anti-GBF1 antibodies specifically caused dissociation of COPI from membranes. These observations strongly suggest that GBF1 regulates COPI membrane recruitment in the early secretory pathway. ..
  28. Balañá M, Niedergang F, Subtil A, Alcover A, Chavrier P, Dautry Varsat A. ARF6 GTPase controls bacterial invasion by actin remodelling. J Cell Sci. 2005;118:2201-10 pubmed
    ..These results indicate that ARF6, which controls membrane delivery during phagocytosis of red blood cells in macrophages, has a different role in the entry of this small bacterium, controlling cytoskeletal reorganization. ..
  29. Hori Y, Kobayashi T, Kikko Y, Kontani K, Katada T. Domain architecture of the atypical Arf-family GTPase Arl13b involved in cilia formation. Biochem Biophys Res Commun. 2008;373:119-24 pubmed publisher
    ..These findings suggest that N and C domains of Arl13b cooperatively regulate its ciliary localization and that N domain-dependent self-association of Arl13b may be important for its function in cilia biogenesis. ..
  30. Dunphy J, Moravec R, Ly K, Lasell T, Melancon P, Casanova J. The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins. Curr Biol. 2006;16:315-20 pubmed
    ..These findings suggest that Arf6 regulates both endocytosis and recycling of beta1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization. ..
  31. Nishiya N, Kiosses W, Han J, Ginsberg M. An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells. Nat Cell Biol. 2005;7:343-52 pubmed
    ..These findings establish a mechanism for the spatial localization of Rac activity to enhance cell migration. ..
  32. Duldulao N, Lee S, Sun Z. Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion. Development. 2009;136:4033-42 pubmed publisher
    ..Together, these results strongly support the hypothesis that JS-related disease (JSRD) is a ciliopathy, or a disease caused by ciliary defects, and that Arl13b functions mainly through the cilium. ..
  33. Nie Z, Hirsch D, Luo R, Jian X, Stauffer S, Cremesti A, et al. A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure and trafficking of epidermal growth factor receptor. Curr Biol. 2006;16:130-9 pubmed
    ..The N-terminal BAR domain of ASAP1 mediates membrane bending and is necessary for ASAP1 function. The Arf dependence of the bending activity is consistent with ASAP1 functioning as an Arf effector. ..
  34. Gillingham A, Munro S. The small G proteins of the Arf family and their regulators. Annu Rev Cell Dev Biol. 2007;23:579-611 pubmed
    ..Here we review what is known about all the members of the Arf family, along with the known regulatory molecules that convert them between GDP- and GTP-bound states. ..
  35. Li J, Ballif B, Powelka A, Dai J, Gygi S, Hsu V. Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration. Dev Cell. 2005;9:663-73 pubmed
    ..These findings advance an understanding of how integrin recycling is achieved during cell migration, and also address a basic issue of how intracellular signaling can interface with transport to achieve regulated recycling. ..
  36. Shmuel M, Santy L, Frank S, Avrahami D, Casanova J, Altschuler Y. ARNO through its coiled-coil domain regulates endocytosis at the apical surface of polarized epithelial cells. J Biol Chem. 2006;281:13300-8 pubmed
    ..We conclude that ARNO acts together with ARF6 to regulate apical endocytosis. ..
  37. Kobayashi T, Hori Y, Ueda N, Kajiho H, Muraoka S, Shima F, et al. Biochemical characterization of missense mutations in the Arf/Arl-family small GTPase Arl6 causing Bardet-Biedl syndrome. Biochem Biophys Res Commun. 2009;381:439-42 pubmed publisher
    ..These findings implicate that Arl6 mutants are destabilized and eliminated by the proteasome in cells, probably due to the altered nucleotide-binding properties. ..
  38. Lundmark R, Doherty G, Vallis Y, Peter B, McMahon H. Arf family GTP loading is activated by, and generates, positive membrane curvature. Biochem J. 2008;414:189-94 pubmed publisher
    ..Arf1 and Arf6 were shown to load GTP in a membrane-curvature-dependent manner and stabilize, or further facilitate, changes in membrane curvature through the insertion of an amphipathic helix. ..
  39. Lay D, Gorgas K, Just W. Peroxisome biogenesis: where Arf and coatomer might be involved. Biochim Biophys Acta. 2006;1763:1678-87 pubmed
  40. Jones M, Caswell P, Norman J. Endocytic recycling pathways: emerging regulators of cell migration. Curr Opin Cell Biol. 2006;18:549-57 pubmed
    ..Recent work provides new insight into the importance of particular recycling events in cell migration within a variety of physiological contexts. ..
  41. Hiroi T, Someya A, Thompson W, Moss J, Vaughan M. GEP100/BRAG2: activator of ADP-ribosylation factor 6 for regulation of cell adhesion and actin cytoskeleton via E-cadherin and alpha-catenin. Proc Natl Acad Sci U S A. 2006;103:10672-7 pubmed
  42. Hyman T, Shmuel M, Altschuler Y. Actin is required for endocytosis at the apical surface of Madin-Darby canine kidney cells where ARF6 and clathrin regulate the actin cytoskeleton. Mol Biol Cell. 2006;17:427-37 pubmed
    ..These observations indicate that concomitant to actin recruitment, the apical clathrin endocytic system is deeply involved in the morphology of the apical plasma membrane. ..
  43. Kametaka S, Mattera R, Bonifacino J. Epidermal growth factor-dependent phosphorylation of the GGA3 adaptor protein regulates its recruitment to membranes. Mol Cell Biol. 2005;25:7988-8000 pubmed
    ..These observations indicate that EGF signaling elicits phosphorylation events that regulate the association of GGA3 with organellar membranes. ..
  44. Koo T, Eipper B, Donaldson J. Arf6 recruits the Rac GEF Kalirin to the plasma membrane facilitating Rac activation. BMC Cell Biol. 2007;8:29 pubmed
    ..Although Kalirin is recruited onto membranes by Arf6-GDP, subsequent Rac activation and membrane ruffling requires Arf6 activation. From these results, we suggest that Arf6 can regulate through its GTPase cycle the activation of Rac. ..
  45. Cohen L, Honda A, Varnai P, Brown F, Balla T, Donaldson J. Active Arf6 recruits ARNO/cytohesin GEFs to the PM by binding their PH domains. Mol Biol Cell. 2007;18:2244-53 pubmed
    ..This interaction was direct and required both inositol phospholipids and GTP. We propose a model of sequential Arf activation at the PM whereby Arf6-GTP recruits ARNO family GEFs for further activation of other Arf isoforms. ..
  46. Price H, Stark M, Smith D. Trypanosoma brucei ARF1 plays a central role in endocytosis and golgi-lysosome trafficking. Mol Biol Cell. 2007;18:864-73 pubmed
    ..We conclude that the essential Golgi-localizing T. brucei ARF1 has a primary role in the maintenance of both post-Golgi transport and endocytosis and that it is significantly divergent from other characterized ARFs. ..
  47. Klein S, Franco M, Chardin P, Luton F. Role of the Arf6 GDP/GTP cycle and Arf6 GTPase-activating proteins in actin remodeling and intracellular transport. J Biol Chem. 2006;281:12352-61 pubmed
    ..Finally, competition experiments conducted in vivo suggest the existence of a membrane receptor for GDP-bound Arf6. ..
  48. Béglé A, Tryoen Toth P, de Barry J, Bader M, Vitale N. ARF6 regulates the synthesis of fusogenic lipids for calcium-regulated exocytosis in neuroendocrine cells. J Biol Chem. 2009;284:4836-45 pubmed publisher
    ..Altogether these data indicate that ARF6 is a critical upstream signaling element in the activation of PLD necessary to produce the fusogenic lipids required for exocytosis. ..
  49. Santy L, Ravichandran K, Casanova J. The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. Curr Biol. 2005;15:1749-54 pubmed
    ..Together, these data suggest that ARNO and ARF6 coordinate with the Dock180/Elmo complex to promote Rac activation at the leading edge of migrating cells. ..
  50. Munro S. The Arf-like GTPase Arl1 and its role in membrane traffic. Biochem Soc Trans. 2005;33:601-5 pubmed
    ..Genetic analysis in a number of species has shown that Arl1 is not essential for exocytosis, but rather suggest that it is required for traffic from endosomes to the Golgi. ..
  51. Suzuki T, Kanai Y, Hara T, Sasaki J, Sasaki T, Kohara M, et al. Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development. Mol Cell Biol. 2006;26:6149-56 pubmed
    ..These results provide evidence that ARF6 is an essential component in the signaling pathway coupling HGF signaling to hepatic cord formation. ..
  52. Wennerberg K, Rossman K, Der C. The Ras superfamily at a glance. J Cell Sci. 2005;118:843-6 pubmed
  53. Li J, Peters P, Bai M, Dai J, Bos E, Kirchhausen T, et al. An ACAP1-containing clathrin coat complex for endocytic recycling. J Cell Biol. 2007;178:453-64 pubmed
    ..These findings not only advance a basic understanding of an early mechanistic step in endocytic recycling but also shed key mechanistic insights into major physiological events for which this transport plays a critical role. ..