Gene Symbol: Arf6
Description: ADP-ribosylation factor 6
Alias: ADP-ribosylation factor 6
Species: rat
Products:     Arf6

Top Publications

  1. Kobayashi H, Fukuda M. Rab35 regulates Arf6 activity through centaurin-?2 (ACAP2) during neurite outgrowth. J Cell Sci. 2012;125:2235-43 pubmed publisher
    ..Although Rab35 and Arf6 were independently reported to regulate the same cellular events, including endocytic recycling, phagocytosis, ..
  2. D SOUZA SCHOREY C, Boshans R, McDonough M, Stahl P, Van Aelst L. A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements. EMBO J. 1997;16:5445-54 pubmed
    The ARF6 GTPase, the least conserved member of the ADP ribosylation factor (ARF) family, associates with the plasma membrane and intracellular endosome vesicles...
  3. Rahajeng J, Giridharan S, Cai B, Naslavsky N, Caplan S. MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. Traffic. 2012;13:82-93 pubmed publisher
    ..Moreover, we demonstrate that Arf6 forms a complex with MICAL-L1 and plays a role in its recruitment to tubular endosomes...
  4. 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
    ..Although both ARF1 and ARF6 were found on peroxisomes, coatomer recruitment only depended on ARF1-GTP...
  5. 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
    The mammalian small GTPase ADP-ribosylation factor 6 (ARF6) plays important roles in a wide variety of cellular events, including endocytosis, actin cytoskeletal reorganization, and phosphoinositide metabolism...
  6. Mitrea D, Grace C, Buljan M, Yun M, Pytel N, Satumba J, et al. Structural polymorphism in the N-terminal oligomerization domain of NPM1. Proc Natl Acad Sci U S A. 2014;111:4466-71 pubmed publisher
    ..We propose that the diverse functional repertoire associated with NPM1 is controlled through a regulated unfolding mechanism signaled through posttranslational modifications and intermolecular interactions...
  7. Chies R, Nobbio L, Edomi P, Schenone A, Schneider C, Brancolini C. Alterations in the Arf6-regulated plasma membrane endosomal recycling pathway in cells overexpressing the tetraspan protein Gas3/PMP22. J Cell Sci. 2003;116:987-99 pubmed
    ..receptor, but instead they trap membrane proteins that normally traffic through the ADP-ribosylation factor 6 (Arf6) endosomal compartment...
  8. Eva R, Crisp S, Marland J, Norman J, Kanamarlapudi V, Ffrench Constant C, et al. ARF6 directs axon transport and traffic of integrins and regulates axon growth in adult DRG neurons. J Neurosci. 2012;32:10352-64 pubmed
    ..Integrins are in ARF6 vesicles during rapid axonal transport and during trafficking in the growth cone...
  9. Rankovic M, Jacob L, Rankovic V, Brandenburg L, Schroder H, Hollt V, et al. ADP-ribosylation factor 6 regulates mu-opioid receptor trafficking and signaling via activation of phospholipase D2. Cell Signal. 2009;21:1784-93 pubmed publisher
    ..HEK) 293 cells and primary cultured cortical neurons as well as by using siRNA technology, we identified the ARF6 protein to be involved in the regulation of MOPr endocytosis...

More Information


  1. Kagan J, Medzhitov R. Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell. 2006;125:943-55 pubmed
    ..TIRAP then functions to facilitate MyD88 delivery to activated TLR4 to initiate signal transduction. These results establish that phosphoinositide-mediated adaptor recruitment initiates a specific signal-transduction pathway. ..
  2. Vitale N, Mawet J, Camonis J, Regazzi R, Bader M, Chasserot Golaz S. The Small GTPase RalA controls exocytosis of large dense core secretory granules by interacting with ARF6-dependent phospholipase D1. J Biol Chem. 2005;280:29921-8 pubmed
    ..We demonstrate that cell stimulation triggers a direct interaction between RalA and ARF6-activated PLD1...
  3. Franssen E, Zhao R, Koseki H, Kanamarlapudi V, Hoogenraad C, Eva R, et al. Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS. J Neurosci. 2015;35:8359-75 pubmed publisher
    ..The directionality of transport is controlled through the activation state of ARF6, with developmental upregulation of the ARF6 GEF ARNO enhancing retrograde transport...
  4. Kim Y, Lee S, Park J, Kim M, Lee B, Hwang D, et al. ADP-ribosylation factor 6 (ARF6) bidirectionally regulates dendritic spine formation depending on neuronal maturation and activity. J Biol Chem. 2015;290:7323-35 pubmed publisher
    Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested...
  5. Jayaram B, Syed I, Kyathanahalli C, Rhodes C, Kowluru A. Arf nucleotide binding site opener [ARNO] promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion in INS 832/13 ?-cells and rat islets. Biochem Pharmacol. 2011;81:1016-27 pubmed publisher
    ..that Arf nucleotide binding site opener [ARNO], a guanine nucleotide-exchange factor [GEF] for the small G-protein Arf6, mediates the functional activation of Arf6, and that ARNO/Arf6 signaling axis, in turn, controls the activation of ..
  6. Meyer M, Déliot N, Chasserot Golaz S, Premont R, Bader M, Vitale N. Regulation of neuroendocrine exocytosis by the ARF6 GTPase-activating protein GIT1. J Biol Chem. 2006;281:7919-26 pubmed
    ..Using chromaffin and PC12 cells, we have recently described that the granule-associated GTPase ARF6 plays a crucial role in exocytosis by activating phospholipase D1 at the plasma membrane and, presumably, promoting ..
  7. Miyazaki H, Yamazaki M, Watanabe H, Maehama T, Yokozeki T, Kanaho Y. The small GTPase ADP-ribosylation factor 6 negatively regulates dendritic spine formation. FEBS Lett. 2005;579:6834-8 pubmed
    ..Here we investigated whether the small GTPase, ADP-ribosylation factor 6 (ARF6), which regulates actin dynamics and peripheral vesicular trafficking, is involved in the regulation of spine ..
  8. Karnik R, Ludlow M, Abuarab N, Smith A, Hardy M, Elliott D, et al. Endocytosis of HERG is clathrin-independent and involves arf6. PLoS ONE. 2013;8:e85630 pubmed publisher
    ..Endocytosis was significantly affected by cholesterol extraction with methyl-?-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP...
  9. Sannerud R, Declerck I, Peric A, Raemaekers T, Menendez G, Zhou L, et al. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proc Natl Acad Sci U S A. 2011;108:E559-68 pubmed publisher
    ..we demonstrate that BACE1 is sorted to early endosomes via a route controlled by the small GTPase ADP ribosylation factor 6 (ARF6)...
  10. Bai M, Gad H, Turacchio G, Cocucci E, Yang J, Li J, et al. ARFGAP1 promotes AP-2-dependent endocytosis. Nat Cell Biol. 2011;13:559-67 pubmed publisher
    ..The role of ARFGAP1 in AP-2-regulated endocytosis has mechanistic parallels with its roles in COPI transport, as both its GAP activity and coat function contribute to promoting AP-2 transport. ..
  11. Ikenouchi J, Umeda M. FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex. Proc Natl Acad Sci U S A. 2010;107:748-53 pubmed publisher
    ..In the present study, we found that activation of Arf6 is spatiotemporally regulated as a downstream signaling pathway of the Par protein complex...
  12. Kobayashi H, Fukuda M. Rab35 establishes the EHD1-association site by coordinating two distinct effectors during neurite outgrowth. J Cell Sci. 2013;126:2424-35 pubmed publisher
    ..Rab35 forms a tripartite complex with MICAL-L1 and centaurin-?2/ACAP2 and recruits them to perinuclear Arf6-positive endosomes in response to nerve growth factor stimulation...
  13. Andreev J, Simon J, Sabatini D, Kam J, Plowman G, Randazzo P, et al. Identification of a new Pyk2 target protein with Arf-GAP activity. Mol Cell Biol. 1999;19:2338-50 pubmed
    ..strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of recombinant Pap protein to Golgi preparations prevented Arf-dependent generation of post-Golgi ..
  14. Ueda T, Hanai A, Takei T, Kubo K, Ohgi M, Sakagami H, et al. EFA6 activates Arf6 and participates in its targeting to the Flemming body during cytokinesis. FEBS Lett. 2013;587:1617-23 pubmed publisher
    The small GTPase Arf6 is transiently associated with the ingressing cleavage furrow and subsequently targeted to the Flemming body during cytokinesis, suggesting its activation around the cleavage furrow...
  15. 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
    ..Using real time FRET (fluorescence resonance energy transfer) measurements, we show here that the GTPase ARF6, potentially involved in the synthesis of these lipids, is activated at the exocytotic sites in PC12 cells ..
  16. Bourmoum M, Charles R, Claing A. The GTPase ARF6 Controls ROS Production to Mediate Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation. PLoS ONE. 2016;11:e0148097 pubmed publisher
    ..We have previously shown that the ADP-ribosylation factor 6 (ARF6), a molecular switch that coordinates intracellular signaling events can be activated by the Ang II receptor (AT1R)...
  17. Yanase Y, Carvou N, Frohman M, Cockcroft S. Reversible bleb formation in mast cells stimulated with antigen is Ca2+/calmodulin-dependent and bleb size is regulated by ARF6. Biochem J. 2009;425:179-93 pubmed publisher
    ..We also examined the requirement for ARF6 (ADP-ribosylation factor 6) and observed that its expression led to an increase in bleb size and a further increase ..
  18. Elagabani M, Briševac D, Kintscher M, Pohle J, Köhr G, Schmitz D, et al. Subunit-selective N-Methyl-d-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation. J Biol Chem. 2016;291:9105-18 pubmed publisher
    ..Here we show that NMDARs control the activity of the small GTPase ADP-ribosylation factor 6 (Arf6) by consecutively recruiting two related brefeldin A-resistant Arf guanine nucleotide exchange factors, BRAG1 and ..
  19. Doroudgar S, Thuerauf D, Marcinko M, Belmont P, Glembotski C. Ischemia activates the ATF6 branch of the endoplasmic reticulum stress response. J Biol Chem. 2009;284:29735-45 pubmed publisher
  20. Anthonio E, Brees C, Baumgart Vogt E, Hongu T, Huybrechts S, Van Dijck P, et al. Small G proteins in peroxisome biogenesis: the potential involvement of ADP-ribosylation factor 6. BMC Cell Biol. 2009;10:58 pubmed publisher
    ..In addition, we provide evidence that a portion of endogenous Arf6, the mammalian orthologue of yeast Arf3, is associated with the cytoplasmic face of rat liver peroxisomes...
  21. al Awar O, Radhakrishna H, Powell N, Donaldson J. Separation of membrane trafficking and actin remodeling functions of ARF6 with an effector domain mutant. Mol Cell Biol. 2000;20:5998-6007 pubmed
    The ADP-ribosylation factor 6 (ARF6) GTPase has a dual function in cells, regulating membrane traffic and organizing cortical actin...
  22. 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 small GTPase Arf6 regulates endocytosis, actin dynamics, and cell adhesion, and one of its major activators is the exchange factor Arf nucleotide-binding site opener (ARNO), also called cytohesin-2 [1, 2]...
  23. Falace A, Buhler E, Fadda M, Watrin F, Lippiello P, Pallesi Pocachard E, et al. TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway. Proc Natl Acad Sci U S A. 2014;111:2337-42 pubmed publisher
    ..We show that in vivo, overexpression of the dominant-negative form of ARF6 rescues the neuronal migration and dendritic outgrowth defects induced by TBC1D24 knockdown, suggesting that ..
  24. Gauthier Campbell C, Bredt D, Murphy T, El Husseini A. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004;15:2205-17 pubmed
    ..Moreover, overexpression of a constitutively active form of ARF6, a GTPase that regulates membrane cycling and dendritic branching reversed the effects of the acylated protein ..
  25. El Annan J, Brown D, Breton S, Bourgoin S, Ausiello D, Marshansky V. Differential expression and targeting of endogenous Arf1 and Arf6 small GTPases in kidney epithelial cells in situ. Am J Physiol Cell Physiol. 2004;286:C768-78 pubmed
    ..immunocytochemistry and Western blotting were performed to characterize the expression and targeting of Arf1 and Arf6 in epithelial cells in situ...
  26. Radhakrishna H, al Awar O, Khachikian Z, Donaldson J. ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements. J Cell Sci. 1999;112 ( Pt 6):855-66 pubmed
    The ARF6 GTPase regulates a novel endosomal-plasma membrane recycling pathway and influences cortical actin remodeling...
  27. Tagliatti E, Fadda M, Falace A, Benfenati F, Fassio A. Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse. elife. 2016;5: pubmed publisher
    ..b>ADP ribosylation factor 6 (Arf6) is a small GTPase known to participate in constitutive trafficking between plasma membrane and ..
  28. Choi S, Ko J, Lee J, Lee H, Kim K, Chung H, et al. ARF6 and EFA6A regulate the development and maintenance of dendritic spines. J Neurosci. 2006;26:4811-9 pubmed
    ..ADP-ribosylation factor 6 (ARF6) is a small GTPase known to regulate actin remodeling and membrane traffic...
  29. Martinu L, Masuda Robens J, Robertson S, Santy L, Casanova J, Chou M. The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6. Mol Cell Biol. 2004;24:9752-62 pubmed
    ..we show that TRE17 (also called Tre-2 and USP6), a founding member of the TBC family, targets the Arf family GTPase Arf6, which regulates plasma membrane-endosome trafficking...
  30. Wan T, Liu T, Zhang H, Tang S, Min W. AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling. J Biol Chem. 2010;285:3750-7 pubmed publisher
    ..We further show that AIP1 is a novel GTPase-activating protein (GAP) for Arf6, a small GTPase regulating cellular PIP(2) production and formation of the TLR4-TIRAP-MyD88 complex...
  31. Hernandez Deviez D, Mackay Sim A, Wilson J. A Role for ARF6 and ARNO in the regulation of endosomal dynamics in neurons. Traffic. 2007;8:1750-64 pubmed
    ..We have shown a regulatory role for ARNO and ARF6 in dendritic branching and axonal elongation and branching during neuritogenesis, particularly with respect to ..
  32. Miyamoto Y, Yamamori N, Torii T, Tanoue A, Yamauchi J. Rab35, acting through ACAP2 switching off Arf6, negatively regulates oligodendrocyte differentiation and myelination. Mol Biol Cell. 2014;25:1532-42 pubmed publisher
    ..We show that Rab35 and its effector, ACAP2, a GTPase-activating protein that switches off Arf6 activity, negatively regulate oligodendrocyte morphological differentiation...
  33. Powner D, Hodgkin M, Wakelam M. Antigen-stimulated activation of phospholipase D1b by Rac1, ARF6, and PKCalpha in RBL-2H3 cells. Mol Biol Cell. 2002;13:1252-62 pubmed
    ..Antigen stimulation of RBL-2H3 cells induces the colocalization of PLD1b with Rac1, ARF6, and PKCalpha at the plasma membrane in actin-rich structures, simultaneously with cooperatively increasing PLD ..
  34. Wolff N, Lee W, Abouhamed M, Thevenod F. Role of ARF6 in internalization of metal-binding proteins, metallothionein and transferrin, and cadmium-metallothionein toxicity in kidney proximal tubule cells. Toxicol Appl Pharmacol. 2008;230:78-85 pubmed publisher
    ..We investigated roles of ARF6, which has been shown to be involved in internalization of ligands and endocytic trafficking in PT cells, following ..
  35. Price S, Nightingale M, Tsuchiya M, Moss J, Vaughan M. Interspecies relationships among ADP-ribosylation factors (ARFs): evidence of evolutionary pressure to maintain individual identities. Mol Cell Biochem. 1996;159:15-23 pubmed
    ..The unusually high degree of conservation of the untranslated regions is consistent with these regions having important regulatory roles and that individual ARFs contain structurally unique elements required for specific functions. ..
  36. Hosaka M, Toda K, Takatsu H, Torii S, Murakami K, Nakayama K. Structure and intracellular localization of mouse ADP-ribosylation factors type 1 to type 6 (ARF1-ARF6). J Biochem. 1996;120:813-9 pubmed
    ..These results suggest that although all the ARF proteins play fundamental and critical roles in cellular function, they are involved in different vesicular transport processes. ..
  37. Hernandez Deviez D, Casanova J, Wilson J. Regulation of dendritic development by the ARF exchange factor ARNO. Nat Neurosci. 2002;5:623-4 pubmed
    Here we analyzed the role of ARF6, a member of the ADP-ribosylation factor (ARF) family of small GTPases, in dendritic arbor development in rat hippocampal neurons in culture...