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PMID: 10075920 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

EFA6, a sec7 domain-containing exchange factor for ARF6, coordinates membrane recycling and actin cytoskeleton organization.

The EMBO journal ·Vol. 18 ·No. 6 ·1999-03-15 ·Pages 1480-91

Franco M, Peters PJ, Boretto J, van Donselaar E, Neri A, D'Souza-Schorey C, Chavrier P

Abstract

We have identified a human cDNA encoding a novel protein, exchange factor for ARF6 (EFA6), which contains Sec7 and pleckstrin homology domains. EFA6 promotes efficient guanine nucleotide exchange on ARF6 and is distinct from the ARNO family of ARF1 exchange factors. The protein localizes to a dense matrix on the cytoplasmic face of plasma membrane invaginations, induced on its expression. We show that EFA6 regulates endosomal membrane recycling and promotes the redistribution of transferrin receptors to the cell surface. Furthermore, expression of EFA6 induces actin-based membrane ruffles that are inhibited by co-expression of dominant-inhibitory mutant forms of ARF6 or Rac1. Our results demonstrate that by catalyzing nucleotide exchange on ARF6 at the plasma membrane and by regulating Rac1 activation, EFA6 coordinates endocytosis with cytoskeletal rearrangements.

MeSH Terms
ADP-Ribosylation Factor 1 ADP-Ribosylation Factors Actins/chemistry,metabolism Amino Acid Sequence Animals CHO Cells Carrier Proteins/chemistry,metabolism Cricetinae Cytoskeleton/ultrastructure DNA, Complementary Fungal Proteins/chemistry GTP-Binding Proteins/chemistry,metabolism Guanine Nucleotide Exchange Factors Humans Kinetics Nerve Tissue Proteins Peptide Elongation Factors/metabolism,physiology Polymerase Chain Reaction Receptors, Transferrin/metabolism Recombinant Proteins/chemistry,metabolism Sequence Alignment Sequence Deletion Sequence Homology, Amino Acid Transfection src Homology Domains
Chemicals
Actins Carrier Proteins DNA, Complementary Fungal Proteins Guanine Nucleotide Exchange Factors Nerve Tissue Proteins PSD protein, human Peptide Elongation Factors Receptors, Transferrin Recombinant Proteins Sec7 guanine nucleotide exchange factors GTP-Binding Proteins ADP-Ribosylation Factor 1 ADP-Ribosylation Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Franco M
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France.
Peters P J
Boretto J
van Donselaar E
Neri A
D'Souza-Schorey C
Chavrier P
References (61)
61 references, click to expand
  1. SEC7 encodes an unusual, high molecular weight protein required for membrane traffic from the yeast Golgi apparatus.
    J Biol Chem. 1988 Aug 25;263(24):11711-7 PMID: 3042778
  2. A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements.
    EMBO J. 1997 Sep 1;16(17):5445-54 PMID: 9312003
  3. Regulated exocytosis in chromaffin cells. A potential role for a secretory granule-associated ARF6 protein.
    J Biol Chem. 1997 Jan 31;272(5):2788-93 PMID: 9006918
  4. Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid.
    Mol Cell Biol. 1997 Mar;17(3):1201-11 PMID: 9032247
  5. Overexpression of the ARF1 exchange factor ARNO inhibits the early secretory pathway and causes the disassembly of the Golgi complex.
    J Cell Sci. 1998 Nov;111 ( Pt 22):3427-36 PMID: 9788883
  6. Myristoylation of ADP-ribosylation factor 1 facilitates nucleotide exchange at physiological Mg2+ levels.
    J Biol Chem. 1995 Jan 20;270(3):1337-41 PMID: 7836400
  7. ADP-ribosylation factor is a subunit of the coat of Golgi-derived COP-coated vesicles: a novel role for a GTP-binding protein.
    Cell. 1991 Oct 18;67(2):239-53 PMID: 1680566
  8. Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase.
    Cell. 1998 Feb 6;92(3):415-23 PMID: 9476900
  9. Identification of a novel Rac1-interacting protein involved in membrane ruffling.
    EMBO J. 1996 Aug 1;15(15):3778-86 PMID: 8670882
  10. Cloning and expression of a cDNA encoding a bovine brain brefeldin A-sensitive guanine nucleotide-exchange protein for ADP-ribosylation factor.
    Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12926-31 PMID: 9371777
  11. ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway.
    J Cell Biol. 1997 Oct 6;139(1):49-61 PMID: 9314528
  12. ARNO3, a Sec7-domain guanine nucleotide exchange factor for ADP ribosylation factor 1, is involved in the control of Golgi structure and function.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9926-31 PMID: 9707577
  13. Functional expression of the human transferrin receptor cDNA in Chinese hamster ovary cells deficient in endogenous transferrin receptor.
    J Cell Biol. 1987 Jul;105(1):207-14 PMID: 3611186
  14. ARNO is a guanine nucleotide exchange factor for ADP-ribosylation factor 6.
    J Biol Chem. 1998 Jan 2;273(1):23-7 PMID: 9417041
  15. Endosome dynamics regulated by a Rho protein.
    Nature. 1996 Dec 5;384(6608):427-32 PMID: 8945468
  16. Nucleotide exchange on ARF mediated by yeast Gea1 protein.
    Nature. 1996 Dec 5;384(6608):479-81 PMID: 8945477
  17. Quantification of low density lipoprotein and transferrin endocytic sorting HEp2 cells using confocal microscopy.
    J Cell Sci. 1994 Aug;107 ( Pt 8):2177-89 PMID: 7983176
  18. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  19. Regulation of receptor-mediated endocytosis by Rho and Rac.
    Nature. 1996 Jul 11;382(6587):177-9 PMID: 8700210
  20. Identification of a novel gene, PSD, adjacent to NFKB2/lyt-10, which contains Sec7 and pleckstrin-homology domains.
    Genomics. 1997 Dec 1;46(2):251-9 PMID: 9417912
  21. The guanine nucleotide exchange factor Tiam1 affects neuronal morphology; opposing roles for the small GTPases Rac and Rho.
    J Cell Biol. 1997 Nov 3;139(3):797-807 PMID: 9348295
  22. Molecular identification of ADP-ribosylation factor mRNAs and their expression in mammalian cells.
    J Biol Chem. 1991 Feb 15;266(5):2772-7 PMID: 1993656
  23. A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+ and the beta-phosphate to destabilize GDP on ARF1.
    EMBO J. 1998 Jul 1;17(13):3651-9 PMID: 9649435
  24. Selective control of membrane ruffling and actin plaque assembly by the Rho GTPases Rac1 and CDC42 in FcepsilonRI-activated rat basophilic leukemia (RBL-2H3) cells.
    J Cell Sci. 1997 Sep;110 ( Pt 18):2215-25 PMID: 9378771
  25. A regulatory role for ARF6 in receptor-mediated endocytosis.
    Science. 1995 Feb 24;267(5201):1175-8 PMID: 7855600
  26. Traffic COPs and the formation of vesicle coats.
    Trends Cell Biol. 1996 Dec;6(12):468-73 PMID: 15157504
  27. Functional compartments of the yeast Golgi apparatus are defined by the sec7 mutation.
    EMBO J. 1989 Sep;8(9):2695-702 PMID: 2684655
  28. Regulation of GRP1-catalyzed ADP ribosylation factor guanine nucleotide exchange by phosphatidylinositol 3,4,5-trisphosphate.
    J Biol Chem. 1998 Jan 23;273(4):1859-62 PMID: 9442017
  29. Subcellular distribution and differential expression of endogenous ADP-ribosylation factor 6 in mammalian cells.
    J Biol Chem. 1998 Feb 13;273(7):4006-11 PMID: 9461590
  30. Regulated exocytosis in chromaffin cells. Translocation of ARF6 stimulates a plasma membrane-associated phospholipase D.
    J Biol Chem. 1998 Jan 16;273(3):1373-9 PMID: 9430671
  31. Phospholipase D: a downstream effector of ARF in granulocytes.
    Science. 1994 Jan 28;263(5146):523-6 PMID: 8290961
  32. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity.
    Cell. 1993 Dec 17;75(6):1137-44 PMID: 8261513
  33. ADP-Ribosylation factor 1 (ARF1) regulates recruitment of the AP-3 adaptor complex to membranes.
    J Cell Biol. 1998 Jul 27;142(2):391-402 PMID: 9679139
  34. A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains.
    Nature. 1996 Dec 5;384(6608):481-4 PMID: 8945478
  35. Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9559-64 PMID: 8790369
  36. Regulatory recruitment of signalling molecules to the cell membrane by pleckstrinhomology domains.
    Trends Cell Biol. 1997 Jun;7(6):237-42 PMID: 17708952
  37. Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines.
    Nature. 1996 Feb 29;379(6568):837-40 PMID: 8587609
  38. Coated vesicle assembly in the Golgi requires only coatomer and ARF proteins from the cytosol.
    Nature. 1993 Aug 19;364(6439):732-4 PMID: 8355790
  39. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase.
    Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 PMID: 3095828
  40. EGF induces recycling membrane to form ruffles.
    Curr Biol. 1998 Jun 4;8(12):721-4 PMID: 9637926
  41. Membrane transport in the endocytic pathway.
    Curr Opin Cell Biol. 1995 Aug;7(4):552-63 PMID: 7495576
  42. Overexpression of wild-type and mutant ARF1 and ARF6: distinct perturbations of nonoverlapping membrane compartments.
    J Cell Biol. 1995 Mar;128(6):1003-17 PMID: 7896867
  43. Structure of the Sec7 domain of the Arf exchange factor ARNO.
    Nature. 1998 Mar 5;392(6671):101-5 PMID: 9510256
  44. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  45. In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella.
    J Cell Biol. 1994 Jun;125(6):1265-74 PMID: 7515888
  46. Aluminum fluoride stimulates surface protrusions in cells overexpressing the ARF6 GTPase.
    J Cell Biol. 1996 Aug;134(4):935-47 PMID: 8769418
  47. Cytokinesis arrest and redistribution of actin-cytoskeleton regulatory components in cells expressing the Rho GTPase CDC42Hs.
    J Cell Sci. 1996 Feb;109 ( Pt 2):367-77 PMID: 8838660
  48. Biochemical dissection of AP-1 recruitment onto Golgi membranes.
    J Cell Biol. 1993 Nov;123(3):561-73 PMID: 8227126
  49. Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor.
    Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1745-8 PMID: 9050849
  50. ARF6 targets recycling vesicles to the plasma membrane: insights from an ultrastructural investigation.
    J Cell Biol. 1998 Feb 9;140(3):603-16 PMID: 9456320
  51. The binding of AP-1 clathrin adaptor particles to Golgi membranes requires ADP-ribosylation factor, a small GTP-binding protein.
    Cell. 1993 Jun 4;73(5):999-1005 PMID: 8500185
  52. The small GTP-binding proteins, Rac and Rho, regulate cytoskeletal organization and exocytosis in mast cells by parallel pathways.
    Mol Biol Cell. 1996 Sep;7(9):1429-42 PMID: 8885237
  53. Hydrolysis of bound GTP by ARF protein triggers uncoating of Golgi-derived COP-coated vesicles.
    J Cell Biol. 1993 Dec;123(6 Pt 1):1365-71 PMID: 8253837
  54. Activation of rat brain phospholipase D by ADP-ribosylation factors 1,5, and 6: separation of ADP-ribosylation factor-dependent and oleate-dependent enzymes.
    Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11718-22 PMID: 7972129
  55. Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains.
    Science. 1997 Mar 28;275(5308):1927-30 PMID: 9072969
  56. Cloning and sequencing of a human cDNA from cytolytic NK/T cells with homology to yeast SEC7.
    Biochim Biophys Acta. 1992 Aug 17;1132(1):75-8 PMID: 1511013
  57. Involvement of the transmembrane protein p23 in biosynthetic protein transport.
    J Cell Biol. 1997 Dec 1;139(5):1119-35 PMID: 9382861
  58. EMB30 is essential for normal cell division, cell expansion, and cell adhesion in Arabidopsis and encodes a protein that has similarity to Sec7.
    Cell. 1994 Jul 1;77(7):1051-62 PMID: 8020095
  59. Membrane traffic during cell locomotion.
    Curr Opin Cell Biol. 1998 Aug;10(4):537-41 PMID: 9719876
  60. ARF: a key regulatory switch in membrane traffic and organelle structure.
    Curr Opin Cell Biol. 1994 Aug;6(4):527-32 PMID: 7986529
  61. The diversity of Rab proteins in vesicle transport.
    Curr Opin Cell Biol. 1997 Aug;9(4):496-504 PMID: 9261061
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.6.1480
Published
1999-03-15
Pages
1480-91
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171237
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.6.1480 PMC Full Text View journal details
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