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PMID: 12505986 Published · ppublish English Journal Article

Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex.

The EMBO journal ·Vol. 22 ·No. 1 ·2003-01-02 ·Pages 78-88

Mattera R, Arighi CN, Lodge R, Zerial M, Bonifacino JS

Abstract

Cargo transfer from trans-Golgi network (TGN)-derived transport carriers to endosomes involves a still undefined set of tethering/fusion events. Here we analyze a molecular interaction that may play a role in this process. We demonstrate that the GGAs, a family of Arf-dependent clathrin adaptors involved in selection of TGN cargo, interact with the Rabaptin-5-Rabex-5 complex, a Rab4/Rab5 effector regulating endosome fusion. These interactions are bipartite: GGA-GAE domains recognize an FGPLV sequence (residues 439-443) in a predicted random coil of Rabaptin-5 (a sequence also recognized by the gamma1- and gamma2-adaptin ears), while GGA-GAT domains bind to the C-terminal coiled-coils of Rabaptin-5. The GGA-Rabaptin-5 interaction decreases binding of clathrin to the GGA-hinge domain, and expression of green fluorescent protein (GFP)-Rabaptin-5 shifts the localization of endogenous GGA1 and associated cargo to enlarged early endosomes. These observations thus identify a binding sequence for GAE/gamma-adaptin ear domains and reveal a functional link between proteins regulating TGN cargo export and endosomal tethering/fusion events.

MeSH Terms
Amino Acid Sequence Binding Sites Biotinylation Clathrin/metabolism Glutathione Transferase/metabolism Guanine Nucleotide Exchange Factors/chemistry,metabolism Humans Mutagenesis Peptide Fragments/chemistry,metabolism Recombinant Fusion Proteins/chemistry,metabolism Vesicular Transport Proteins/chemistry,metabolism trans-Golgi Network/metabolism,ultrastructure
Chemicals
Clathrin Guanine Nucleotide Exchange Factors Peptide Fragments RABEP1 protein, human RABGEF1 protein, human Recombinant Fusion Proteins Vesicular Transport Proteins Glutathione Transferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mattera Rafael
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Arighi Cecilia N
Lodge Robert
Zerial Marino
Bonifacino Juan S
References (40)
40 references, click to expand
  1. Gamma-adaptin interacts directly with Rabaptin-5 through its ear domain.
    J Biochem. 2002 Mar;131(3):327-36 PMID: 11872161
  2. Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly.
    Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8907-12 PMID: 10430869
  3. Accessory protein recruitment motifs in clathrin-mediated endocytosis.
    Structure. 2002 Jun;10(6):797-809 PMID: 12057195
  4. Human rabaptin-5 is selectively cleaved by caspase-3 during apoptosis.
    J Biol Chem. 1999 Dec 31;274(53):37583-90 PMID: 10608812
  5. Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles.
    Biochem J. 2000 Mar 15;346 Pt 3:593-601 PMID: 10698684
  6. Vear, a novel Golgi-associated protein with VHS and gamma-adaptin "ear" domains.
    J Biol Chem. 2000 Mar 10;275(10):7176-83 PMID: 10702286
  7. A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.
    J Cell Biol. 2000 Apr 3;149(1):67-80 PMID: 10747088
  8. GGAs: a family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex.
    J Cell Biol. 2000 Apr 3;149(1):81-94 PMID: 10747089
  9. A family of ADP-ribosylation factor effectors that can alter membrane transport through the trans-Golgi.
    Mol Biol Cell. 2000 Apr;11(4):1241-55 PMID: 10749927
  10. Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA proteins that interact with gamma-synergin.
    Biochem Biophys Res Commun. 2000 May 19;271(3):719-25 PMID: 10814529
  11. Accessory factors in clathrin-dependent synaptic vesicle endocytosis.
    Nat Rev Neurosci. 2000 Dec;1(3):161-72 PMID: 11257904
  12. The GGAs promote ARF-dependent recruitment of clathrin to the TGN.
    Cell. 2001 Apr 6;105(1):93-102 PMID: 11301005
  13. Signal-binding specificity of the mu4 subunit of the adaptor protein complex AP-4.
    J Biol Chem. 2001 Apr 20;276(16):13145-52 PMID: 11139587
  14. Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery.
    J Cell Biol. 2001 May 28;153(5):1111-20 PMID: 11381094
  15. Sorting of mannose 6-phosphate receptors mediated by the GGAs.
    Science. 2001 Jun 1;292(5522):1712-6 PMID: 11387475
  16. Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor.
    Science. 2001 Jun 1;292(5522):1716-8 PMID: 11387476
  17. Yeast Gga coat proteins function with clathrin in Golgi to endosome transport.
    Mol Biol Cell. 2001 Jun;12(6):1885-96 PMID: 11408593
  18. Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex.
    Mol Biol Cell. 2001 Jul;12(7):2219-28 PMID: 11452015
  19. Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains.
    J Biol Chem. 2001 Jul 27;276(30):28541-5 PMID: 11390366
  20. Adaptins: the final recount.
    Mol Biol Cell. 2001 Oct;12(10):2907-20 PMID: 11598180
  21. Structural requirements for function of yeast GGAs in vacuolar protein sorting, alpha-factor maturation, and interactions with clathrin.
    Mol Cell Biol. 2001 Dec;21(23):7981-94 PMID: 11689690
  22. Mosaic organization of the endocytic pathway.
    Exp Cell Res. 2002 Jan 1;272(1):8-14 PMID: 11740860
  23. Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes.
    Nat Cell Biol. 2002 Feb;4(2):124-33 PMID: 11788822
  24. Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains.
    Nature. 2002 Feb 21;415(6874):933-7 PMID: 11859375
  25. Structural basis for recognition of acidic-cluster dileucine sequence by GGA1.
    Nature. 2002 Feb 21;415(6874):937-41 PMID: 11859376
  26. Autoinhibition of the ligand-binding site of GGA1/3 VHS domains by an internal acidic cluster-dileucine motif.
    Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8072-7 PMID: 12060753
  27. Structural basis for the accessory protein recruitment by the gamma-adaptin ear domain.
    Nat Struct Biol. 2002 Jul;9(7):527-31 PMID: 12042876
  28. Multiple Rabaptin-5-like transcripts.
    Gene. 2002 Jun 12;292(1-2):191-7 PMID: 12119113
  29. Gamma-adaptin appendage domain: structure and binding site for Eps15 and gamma-synergin.
    Structure. 2002 Aug;10(8):1139-48 PMID: 12176391
  30. Morphology and dynamics of clathrin/GGA1-coated carriers budding from the trans-Golgi network.
    Mol Biol Cell. 2003 Apr;14(4):1545-57 PMID: 12686608
  31. Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion.
    Cell. 1995 Nov 3;83(3):423-32 PMID: 8521472
  32. AP-3: an adaptor-like protein complex with ubiquitous expression.
    EMBO J. 1997 Mar 3;16(5):917-28 PMID: 9118953
  33. A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function.
    Cell. 1997 Sep 19;90(6):1149-59 PMID: 9323142
  34. Cleavage of rabaptin-5 blocks endosome fusion during apoptosis.
    EMBO J. 1997 Oct 15;16(20):6182-91 PMID: 9321397
  35. Neurocrescin: a novel neurite-outgrowth factor secreted by muscle after denervation.
    Neuroreport. 1997 Nov 10;8(16):3649-54 PMID: 9427343
  36. Two distinct effectors of the small GTPase Rab5 cooperate in endocytic membrane fusion.
    EMBO J. 1998 Apr 1;17(7):1930-40 PMID: 9524116
  37. Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound Rab4 and Rab5.
    EMBO J. 1998 Apr 1;17(7):1941-51 PMID: 9524117
  38. Association of the AP-3 adaptor complex with clathrin.
    Science. 1998 Apr 17;280(5362):431-4 PMID: 9545220
  39. A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain.
    Cell. 1999 Jun 11;97(6):805-15 PMID: 10380931
  40. Gamma-synergin: an EH domain-containing protein that interacts with gamma-adaptin.
    J Cell Biol. 1999 Sep 6;146(5):993-1004 PMID: 10477754
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg015
Published
2003-01-02
Pages
78-88
Language
English
Region
England
NLM ID
8208664
PMCID
PMC140067
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg015 PMC Full Text View journal details
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