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PMID: 20228810 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN.

Nature cell biology ·Vol. 12 ·No. 4 ·2010-04-00 ·Pages 330-40

Anitei M, Stange C, Parshina I, Baust T, Schenck A, Raposo G, Kirchhausen T, Hoflack B

Abstract

Actin dynamics is a tightly regulated process involved in various cellular events including biogenesis of clathrin-coated, AP-1 (adaptor protein 1)-coated transport carriers connecting the trans-Golgi network (TGN) and the endocytic pathway. However, the mechanisms coordinating coat assembly, membrane and actin remodelling during post-TGN transport remain poorly understood. Here we show that the Arf1 (ADP-ribosylation factor 1) GTPase synchronizes the TGN association of clathrin-AP-1 coats and protein complexes comprising CYFIP (cytoplasmic fragile-X mental retardation interacting protein; Sra, PIR121), a clathrin heavy chain binding protein associated with mental retardation. The Rac1 GTPase and its exchange factor beta-PIX (PAK-interacting exchange factor) activate these complexes, allowing N-WASP-dependent and Arp2/3-dependent actin polymerization towards membranes, thus promoting tubule formation. These phenomena can be recapitulated with synthetic membranes. This protein-network-based mechanism facilitates the sequential coordination of Arf1-dependent membrane priming, through the recruitment of coats and CYFIP-containing complexes, and of Rac1-dependent actin polymerization, and provides complementary but independent levels of regulation during early stages of clathrin-AP1-coated carrier biogenesis.

MeSH Terms
ADP-Ribosylation Factor 1/genetics,metabolism Actin-Related Protein 2-3 Complex/metabolism Actins/metabolism Adaptor Protein Complex 1/genetics,metabolism Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Brain/metabolism COS Cells Cell Fractionation Chlorocebus aethiops Clathrin-Coated Vesicles/metabolism Endocytosis Guanine Nucleotide Exchange Factors/metabolism HeLa Cells Humans Models, Biological Protein Transport RNA Interference Rho Guanine Nucleotide Exchange Factors Swine Time Factors Transfection Wiskott-Aldrich Syndrome Protein, Neuronal/metabolism rac1 GTP-Binding Protein/genetics,metabolism trans-Golgi Network/metabolism
Chemicals
ARHGEF7 protein, human Actin-Related Protein 2-3 Complex Actins Adaptor Protein Complex 1 Adaptor Proteins, Signal Transducing CYFIP1 protein, human CYFIP2 protein, human Guanine Nucleotide Exchange Factors RAC1 protein, human Rho Guanine Nucleotide Exchange Factors WASL protein, human Wiskott-Aldrich Syndrome Protein, Neuronal ADP-Ribosylation Factor 1 rac1 GTP-Binding Protein
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Anitei Mihaela
Biotechnology Center, Dresden University of Technology, Tatzberg 47-51, 01307 Dresden, Germany.
Stange Christoph
Parshina Irina
Baust Thorsten
Schenck Annette
Raposo Graça
Kirchhausen Tomas
Hoflack Bernard
References (63)
63 references, click to expand
  1. Cdc42 controls secretory and endocytic transport to the basolateral plasma membrane of MDCK cells.
    Nat Cell Biol. 1999 May;1(1):8-13 PMID: 10559857
  2. WAVE/SCAR, a multifunctional complex coordinating different aspects of neuronal connectivity.
    Dev Biol. 2004 Oct 15;274(2):260-70 PMID: 15385157
  3. Selective alterations in biosynthetic and endocytic protein traffic in Madin-Darby canine kidney epithelial cells expressing mutants of the small GTPase Rac1.
    Mol Biol Cell. 2000 Jan;11(1):287-304 PMID: 10637309
  4. Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape.
    J Cell Biol. 2000 Oct 2;151(1):187-98 PMID: 11018064
  5. Localized Rac activation dynamics visualized in living cells.
    Science. 2000 Oct 13;290(5490):333-7 PMID: 11030651
  6. A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8844-9 PMID: 11438699
  7. Polarized dendritic transport and the AP-1 mu1 clathrin adaptor UNC-101 localize odorant receptors to olfactory cilia.
    Neuron. 2001 Aug 2;31(2):277-87 PMID: 11502258
  8. Golgi vesicle proteins are linked to the assembly of an actin complex defined by mAbp1.
    Mol Biol Cell. 2002 Feb;13(2):621-31 PMID: 11854417
  9. Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.
    Nature. 2002 Aug 15;418(6899):790-3 PMID: 12181570
  10. Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits.
    Nat Cell Biol. 2002 Sep;4(9):691-8 PMID: 12198492
  11. Visualization of TGN to endosome trafficking through fluorescently labeled MPR and AP-1 in living cells.
    Mol Biol Cell. 2003 Jan;14(1):142-55 PMID: 12529433
  12. Mannose 6-phosphate receptors: new twists in the tale.
    Nat Rev Mol Cell Biol. 2003 Mar;4(3):202-12 PMID: 12612639
  13. CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein.
    Neuron. 2003 Jun 19;38(6):887-98 PMID: 12818175
  14. Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network.
    Hum Mol Genet. 2003 Oct 1;12(19):2449-56 PMID: 12915445
  15. The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains.
    J Cell Biol. 2003 Oct 27;163(2):351-62 PMID: 14581457
  16. Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions.
    Curr Biol. 2003 Oct 28;13(21):1867-75 PMID: 14588242
  17. The mechanisms of vesicle budding and fusion.
    Cell. 2004 Jan 23;116(2):153-66 PMID: 14744428
  18. Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation.
    EMBO J. 2004 Feb 25;23(4):749-59 PMID: 14765121
  19. RNAi-mediated Hip1R silencing results in stable association between the endocytic machinery and the actin assembly machinery.
    Mol Biol Cell. 2004 Apr;15(4):1666-79 PMID: 14742709
  20. Purification and architecture of the ubiquitous Wave complex.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4379-83 PMID: 15070726
  21. Recycling endosomes supply AMPA receptors for LTP.
    Science. 2004 Sep 24;305(5692):1972-5 PMID: 15448273
  22. Differential sorting of lysosomal enzymes in mannose 6-phosphate receptor-deficient fibroblasts.
    EMBO J. 1994 Aug 1;13(15):3430-7 PMID: 8062819
  23. Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes.
    Nature. 1997 Jan 16;385(6613):265-9 PMID: 9000076
  24. Mannose 6-phosphate receptors regulate the formation of clathrin-coated vesicles in the TGN.
    J Cell Biol. 1997 Apr 21;137(2):335-45 PMID: 9128246
  25. p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase.
    J Biol Chem. 1998 Jan 2;273(1):291-5 PMID: 9417078
  26. PAK3 mutation in nonsyndromic X-linked mental retardation.
    Nat Genet. 1998 Sep;20(1):25-30 PMID: 9731525
  27. Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics.
    Nat Cell Biol. 2005 Apr;7(4):353-64 PMID: 15793564
  28. Actin and Arf1-dependent recruitment of a cortactin-dynamin complex to the Golgi regulates post-Golgi transport.
    Nat Cell Biol. 2005 May;7(5):483-92 PMID: 15821732
  29. Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells.
    Cell. 2005 May 20;121(4):593-606 PMID: 15907472
  30. Abi activates WASP to promote sensory organ development.
    Nat Cell Biol. 2005 Oct;7(10):977-84 PMID: 16155589
  31. Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes.
    Nat Cell Biol. 2005 Oct;7(10):969-76 PMID: 16155590
  32. Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro.
    Nat Chem Biol. 2006 Jan;2(1):39-46 PMID: 16408091
  33. Life of a clathrin coat: insights from clathrin and AP structures.
    Nat Rev Mol Cell Biol. 2006 Jan;7(1):32-44 PMID: 16493411
  34. Actin dynamics at the Golgi complex in mammalian cells.
    Curr Opin Cell Biol. 2006 Apr;18(2):168-78 PMID: 16488588
  35. Proteomic analysis of adaptor protein 1A coats selectively assembled on liposomes.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3159-64 PMID: 16492770
  36. ARF proteins: roles in membrane traffic and beyond.
    Nat Rev Mol Cell Biol. 2006 May;7(5):347-58 PMID: 16633337
  37. Harnessing actin dynamics for clathrin-mediated endocytosis.
    Nat Rev Mol Cell Biol. 2006 Jun;7(6):404-14 PMID: 16723976
  38. Vesicle formation at the plasma membrane and trans-Golgi network: the same but different.
    Science. 2006 Sep 15;313(5793):1591-4 PMID: 16973870
  39. Bar domain proteins: a role in tubulation, scission and actin assembly in clathrin-mediated endocytosis.
    Trends Cell Biol. 2006 Oct;16(10):493-8 PMID: 16949824
  40. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton.
    Nat Rev Mol Cell Biol. 2007 Jan;8(1):37-48 PMID: 17183359
  41. Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation.
    Am J Hum Genet. 2006 Dec;79(6):1119-24 PMID: 17186471
  42. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins.
    Curr Biol. 2007 Apr 3;17(7):592-8 PMID: 17346966
  43. The Prader-Willi phenotype of fragile X syndrome.
    J Dev Behav Pediatr. 2007 Apr;28(2):133-8 PMID: 17435464
  44. The golgi comprises a paired stack that is separated at G2 by modulation of the actin cytoskeleton through Abi and Scar/WAVE.
    Dev Cell. 2007 Jun;12(6):901-15 PMID: 17543863
  45. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors.
    Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15537-42 PMID: 17881561
  46. cdc42 regulates the exit of apical and basolateral proteins from the trans-Golgi network.
    EMBO J. 2001 May 1;20(9):2171-9 PMID: 11331583
  47. Clathrin light chains function in mannose phosphate receptor trafficking via regulation of actin assembly.
    Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):168-73 PMID: 18165318
  48. Binding of cargo sorting signals to AP-1 enhances its association with ADP ribosylation factor 1-GTP.
    J Cell Biol. 2008 Feb 11;180(3):467-72 PMID: 18250197
  49. Motor protein-dependent transport of AMPA receptors into spines during long-term potentiation.
    Nat Neurosci. 2008 Apr;11(4):457-66 PMID: 18311135
  50. Protein networks supporting AP-3 function in targeting lysosomal membrane proteins.
    Mol Biol Cell. 2008 May;19(5):1942-51 PMID: 18287518
  51. Clinical, cellular, and neuropathological consequences of AP1S2 mutations: further delineation of a recognizable X-linked mental retardation syndrome.
    Hum Mutat. 2008 Jul;29(7):966-74 PMID: 18428203
  52. WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER to Golgi transport.
    Cell. 2008 Jul 11;134(1):148-61 PMID: 18614018
  53. FMRP acts as a key messenger for dopamine modulation in the forebrain.
    Neuron. 2008 Aug 28;59(4):634-47 PMID: 18760699
  54. LIM kinase 1 and cofilin regulate actin filament population required for dynamin-dependent apical carrier fission from the trans-Golgi network.
    Mol Biol Cell. 2009 Jan;20(1):438-51 PMID: 18987335
  55. Clathrin adaptor AP-1 complex excludes multiple postsynaptic receptors from axons in C. elegans.
    Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1632-7 PMID: 19164532
  56. Faciogenital dysplasia protein (FGD1) regulates export of cargo proteins from the golgi complex via Cdc42 activation.
    Mol Biol Cell. 2009 May;20(9):2413-27 PMID: 19261807
  57. ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex.
    Nat Cell Biol. 1999 Sep;1(5):280-7 PMID: 10559940
  58. Neural Wiskott Aldrich Syndrome Protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts.
    Eur J Cell Biol. 2004 Feb;83(1):13-8 PMID: 15085951
  59. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor.
    Proc Natl Acad Sci U S A. 2004 May 18;101(20):7618-23 PMID: 15128949
  60. Actin dynamics coupled to clathrin-coated vesicle formation at the trans-Golgi network.
    J Cell Biol. 2004 Jun 21;165(6):781-8 PMID: 15210728
  61. The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors.
    Cell Signal. 2004 Sep;16(9):1001-11 PMID: 15212761
  62. SNAREs prefer liquid-disordered over "raft" (liquid-ordered) domains when reconstituted into giant unilamellar vesicles.
    J Biol Chem. 2004 Sep 3;279(36):37951-5 PMID: 15226320
  63. Endocytosis by random initiation and stabilization of clathrin-coated pits.
    Cell. 2004 Sep 3;118(5):591-605 PMID: 15339664
Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2034
Published
2010-04-00
Epub
2010-00-14
Pages
330-40
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3241509
Subset
IM
Grants
NIGMS NIH HHS · R01 GM075252 · United States
NIGMS NIH HHS · R01 GM075252-04 · United States
NIGMS NIH HHS · GM075252 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1038/ncb2034 PMC Full Text View journal details
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