The role of ARF and Rab GTPases in membrane transport

Current Opinion in Cell Biology

Volumn 11, Issue 4, 1999, Pages 466-475

  Chavrier, Philippe ^a   Goud, Bruno ^b  

^a INSERM   (France)

^b INSTITUT CURIE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATE; RAB PROTEIN;

ADENOSINE DIPHOSPHATE RIBOSYLATION; EUKARYOTIC CELL; INTRACELLULAR TRANSPORT; MEMBRANE TRANSPORT; MEMBRANE VESICLE; PRIORITY JOURNAL; PROTEIN FAMILY; REVIEW;

EID: 0033180113     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(99)80067-2     Document Type: Article

References (77)

1. Schekman R, Orci L: Coat proteins and vesicle budding. Science 1996, 271:1526-1533.
2. Rothman JE: The protein machinery of vesicle budding and fusion. Protein Sci 1996, 5:185-194.
3. Ooi CE, Dell'Angelica EC, Bonifacino JS: ADP-ribosylation factor 1 (ARF1) regulates recruitment of the AP-3 adaptor complex to membranes. J Cell Biol 1998, 142:391-402.
4. Paris S, Beraud-Dufour S, Robineau S, Bigay J, Antonny B, Chabre M, Chardin P: Role of protein-phospholipid interactions in the activation of ARF1 by the guanine nucleotide exchange factor arno. J Biol Chem 1997, 272:22221-22226.
5. Peyroche A, Paris S, Jackson CL: Nucleotide exchange on ARF mediated by yeast Gea1 protein. Nature 1996, 384:479-481.
6. Chardin P, Paris S, Antonny B, Robineau S, Béraud-Dufour S, Jackson CL, Chabre M: A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains. Nature 1996, 384:481-484.
7. Sata M, Donaldson JG, Moss J, Vaughan M: Brefeldin A-inhibited guanine nucleotide-exchange activity of Sec7 domain from yeast Sec7 with yeast and mammalian ADP ribosylation factors. Proc Natl Acad Sci USA 1998, 95:4204-4208.
8. Meacci E, Tsai SC, Adamik R, Moss J, Vaughan M: Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor. Proc Natl Acad Sci USA 1997, 94:1745-1748.
9. Klarlund JK, Guilherme A, Holik JJ, Virbasius JV, Chawla A, Czech MP: Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains. Science 1997, 275:1927-1930.
10. Franco M, Boretto J, Robineau S, Monier S, Goud B, Chardin P, Chavrier P: 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 USA 1998, 95:9926-9931.
11. Mossessova E, Gulbis JM, Goldberg J: Structure of the guanine nucleotide exchange factor Sec7 domain of human Arno and analysis of the interaction with ARF GTPase. Cell 1998, 92:415-423. The authors have determined the crystal structure of the Sec7 domain of human ARNO (23 kDa). It shows a domain of 10 α-helices with a hydrophobic groove for interaction with ARF1. The edges of the groove are formed by two amino acid sequences, which are conserved in all Sec7 domains.
12. Cherfils J, Menetrey J, Mathieu M, Le Bras G, Robineau S, Beraud Dufour S, Antonny B, Chardin P: Structure of the Sec7 domain of the Arf exchange factor ARNO. Nature 1998, 392:101-105. See annotation [11•].
13. 2+ concentration).
14. 2+ in the nucleotide binding pocket of ARF1 and dissociation of bound GDP is further favored by the repulsive effect of the negatively charged sidechain of a conserved glutamate residue of the Sec7 domain (corresponding to Glu156 of human ARNO).
15. Morinaga N, Moss J, Vaughan M: 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 USA 1997, 94:12926-12931.
16. Sata M, Moss J, Vaughan M: Structural basis for the inhibitory effect of brefeldin A on guanine nucleotide-exchange proteins for ADP-ribosylation factors. Proc Natl Acad Sci USA 1999, 96:2752-2757. The authors have constructed chimeric proteins composed of segments of the Sec7 domains of yeast Sec7 (BFA-sensitive) and human Cytohesin-1 (BFA-resistant) to identify the structural basis of BFA-sensitivity. Substitution of two residues of Cytohesin-1 (Ser199, Pro209 - present in all BFA-resistant GEFs) with the corresponding amino acids of yeast Sec7 (Asp965, Met975 - conserved in all BFA-sensitive GEFs) is sufficient to confer BFA- sensitivity to the Sec7 domain of Cytohesin-1.
17. Peyroche A, Antonny B, Robineau S, Acker J, Cherfils J, Jackson CL: Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex: Involvement of specific residues of the sec7 domain. Mol Cell 1999, 3:275-285. GEA1 is an yeast gene encoding a BFA-sensitive Sec7 domain GEF (see [5]). The authors have used a genetic approach to identify mutations in GEA1 that confers BFA resistance in vivo (i.e. growth in the presence of BFA). Residues that are critical for BFA-sensitivity are all located in the region of the Sec7 domain that interacts with ARF1 and are not conserved in BFA-resistant ARNO-like GEFs (note that this region overlaps with the one identified in [16•]). Interestingly, biochemical procedures demonstrated that BFA exerts its inhibitory effect by binding to and stabilizing an abortive complex between ARF1-GDP and the Sec7 domain.
18. Monier S, Chardin P, Robineau S, Goud B: Overexpression of the ARF1 exchange factor ARNO inhibits the early secretory pathway and causes the disassembly of the Golgi complex. J Cell Sci 1998, 111:3427-3436.
19. Spang A, Matsuoka K, Hamamoto S, Schekman R, Orci L: Coatomer, Arf1p, and nucleotide are required to bud coat protein complex I- Coated vesicles from large synthetic liposomes. Proc Natl Acad Sci USA 1998, 95:11199-11204. What are the minimal requirements for COPI-coated vesicle budding? The authors succeeded in reconstituting the budding of small coated vesicles (<70 nm) by incubating liposomes of chemically defined composition (similar to yeast ER membranes) with purified, myristoylated ARF1·GTP and coatomer. Furthermore, this paper shows that acidic phospholipids such as phosphatidic acid (PA) are not sufficient to trigger coat protein recruitment but might promote coatomer binding in the presence of ARF1·GTP. These results demonstrate a direct role for ARF1 in coatomer recruitment to membranes and refute the hypothesis that ARF1 is acting as an activator of PLD- mediated PA production that was proposed to initiate coat protein binding and vesicle formation.
20. Zhao L, Helms JB, Brugger B, Harter C, Martoglio B, Graf R, Brunner J, Wieland FT: Direct and GTP-dependent interaction of ADP ribosylation factor 1 with coatomer subunit beta. Proc Natl Acad Sci USA 1997, 94:4418-4423.
21. Bremser M, Nickel W, Schweikert M, Ravazzola M, Amherdt M, Hughes CA, Sollner TH, Rothman JE, Wieland FT: Coupling of coat assembly and vesicle budding to packaging of putative cargo receptors. Cell 1999, 96:495-506. In an assay that reconstitutes COPI-coated vesicle formation, the authors have explored the function of transmembrane proteins in coatomer recruitment. A peptide corresponding to the cytoplasmic tail of p23 - a putative transmembrane cargo receptor - was coupled to a lipid and this lipopeptide included during the preparation of liposomes of composition mimicking mammalian Golgi membranes. Budding of COPI-coated vesicles required the presence of ARF1·GTP and coatomer added to the p23 lipopeptide- containing liposomes. Budding necessitates the presence of an intact KKXX (in the single letter code for amino acids where X is any amino acid) dibasic motif in the p23 cytoplasmic peptide that is known to bind the γ-COP subunit of coatomer. These results provide a strong indication that coatomer recruitment to Golgi membranes results from a bivalent interaction of coatomer with ARF1-GTP and the cytoplasmic tails of membrane cargo and putative cargo receptors.
22. Springer S, Schekman R: Nucleation of COPII vesicular coat complex by endoplasmic reticulum to Golgi vesicle SNAREs. Science 1998, 281:698-700.
23. Moss J, Vaughan M: Molecules in the ARF orbit J Biol Chem 1998, 273:21431-21434.
24. Aoe T, Cukierman E, Lee A, Cassel D, Peters PJ, Hsu VW: The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a gtpase-activating protein for ARF1. EMBO J 1997, 16:7305-7316.
25. Goldberg J: Structural and functional analysis of the ARF1 ARFGAP complex reveals a role for coatomer in GTP hydrolysis. Cell 1999, 96:893-902. This paper reports the crystal structure (1.95 Å resolution) of ARF1·GDP bound to the catalytic domain of ARF·GAP (residues 6-136). Like other GAPs for small GTP-binding proteins, ARF·GAP acts by stabilizing the switch 2 region of ARF1 to position Glu71 to participate in the hydrolysis reaction. In contrast to other GAPs, however, the GAP binding site does not overlap with the effector binding site on ARF1, nor does ARF·GAP provide any residues participating in hydrolysis. Furthermore, adding coatomer to ARF1·GTP and ARF·GAP accelerates hydrolysis by three orders of magnitude. The proposal of the author is that, in this tripartite complex, the coatomer supplies the residues that enter the active site and accelerate hydrolysis.
26. D'Souza-Schorey C, Van Donselaar E, Hsu VW, Yang C, Stahl PD, Peters PJ: ARF6 targets recycling vesicles to the plasma membrane: Insights from an ultrastructural investigation. J Cell Biol 1998, 140:603-616. The authors have used cryo-immunogold electron microscopy to analyze the intracellular distribution of ARF6 and ARF6 mutant forms in transfected CHO cells. At levels of expression close to that of the endogenous protein, ARF6 and a GTP-binding-defective mutant colocalize with the transferrin receptor and cellubrevin to the pericentriolar recycling compartment. In contrast, a GTP- bound mutant accumulates at the plasma membrane where it induces extensive membrane invaginations. Therefore, depending on its nucleotide status, ARF6 appears to cycle between recycling endosomes and the plasma membrane and might serve to regulate the outward flow of recycling membrane.
27. Radhakrishna H, Donaldson JG: ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway. J Cell Biol 1997, 139:49-61.
28. D'Souza-Schorey C, Boshans RL, McDonough M, Stahl PD, Van Aelst L: A role for POR1, a rac1-interacting protein, in ARF6- Mediated cytoskeletal rearrangements. EMBO J 1997, 16:5445-5454.
29. Song J, Khachikian Z, Radhakrishna H, Donaldson JG: Localization of endogenous ARF6 to sites of cortical actin rearrangement and involvement of ARF6 in cell spreading. J Cell Sci 1998, 111:2257-2267.
30. Caumont AS, Galas MC, Vitale N, Aunis D, Bader MF: Regulated exocytosis in chromaffin cells. Translocation of ARF6 stimulates a plasma membrane-associated phospholipase D. J Biol Chem 1998, 273:1373-1379.
31. Van Aelst L, D'Souza-Schorey C: Rho GTPases and signaling networks. Genes Dev 1997, 11:2295-2322.
32. Radhakrishna H, Al-Awar O, Khachikian Z, Donaldson JG: ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements. J Cell Sci 1999, 112:855-866. The authors show that ARF6 and Rac1 (a member of the Rho subfamily of Ras-related GTP-binding protein involved in the regulation of actin-based membrane ruffling) colocalize in the perinuclear recycling endosomal compartment. Evidence is presented that Rac1-induced membrane ruffling requires the activity of ARF6.
33. Frank S, Upender S, Hansen SH, Casanova JE: ARNO is a guanine nucleotide exchange factor for adp-ribosylation factor 6. J Biol Chem 1998, 273:23-27.
34. Frank SR, Hatfield JC, Casanova JE: Remodeling of the actin cytoskeleton is coordinately regulated by protein kinase C and the ADP-ribosylation factor nucleotide exchange factor ARNO. Mol Biol Cell 1998, 9:3133-3146.
35. Klarlund JK, Rameh LE, Cantley LC, Buxton JM, Holik JJ, Sakelis C, Patki V, Corvera S, Czech MP: Regulation of GRP1-catalyzed ADP ribosylation factor guanine nucleotide exchange by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1998, 273:1859-1862.
36. Venkateswarlu K, Oatey PB, Tavare JM, Cullen PJ: Insulin-dependent translocation of ARNO to the plasma membrane of adipocytes requires phosphatidylinositol 3-kinase. Curr Biol 1998, 8:463-466.
37. Pacheco-Rodriguez G, Meacci E, Vitale N, Moss J, Vaughan M: Guanine nucleotide exchange on ADP-ribosylation factors catalyzed by cytohesin-1 and its Sec7 domain. J Biol Chem 1998, 273:26543-26548.
38. Franco M, Peters PJ, Boretto J, Van Donselaar E, Neri A, D'Souza Schorey C, Chavrier P: EFA6, a Sec7 domain-containing exchange factor for ARF6, coordinates membrane recycling and actin cytoskeleton organization. EMBO J 1999, 18:1480-1491. The authors have identified the first Sec7- and PH-domain-containing GEF, termed EFA6, as a specific activator of ARF6. Overexpressed EFA6 localizes to the cytoplasmic face of actin-based plasma membrane ruffles, which are induced on its expression. As previously shown for ARF6, EFA6 regulates transferrin receptor trafficking. EFA6 might co-ordinate membrane recycling in the endocytic pathway with cytoskeletal rearrangements.
39. Lazar T, Gotte M, Gallwitz D: Vesicular transport: How many Ypt/Rab-GTPases make a eukaryotic cell? Trends Biochem Sci 1997, 22:468-472.
40. Mori T, Fukuda Y, Kuroda H, Matsumura T, Ota S, Sugimoto T, Nakamura Y, Inazawa J: Cloning and characterization of a novel Rab-family gene, Rab36, within the region at 22q11.2 that is homozygously deleted in malignant rhabdoid tumors. Biochem Biophys Res Commun 1999, 254:594-600.
41. Zheng JY, Koda T, Fujiwara T, Kishi M, Ikehara Y, Kakinuma M: A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized to the medial Golgi cisternae. J Cell Sci 1998, 111:1061-1069.
42. Schimmoller F, Simon l, Pfeffer SR: Rab GTPases, directors of vesicle docking. J Biol Chem 1998, 273:22161-22164.
43. Martinez O, Goud B: Rab proteins. Biochim Biophys Acta 1998, 1404:101-112.
44. Gonzalez L Jr, Scheller RH: Regulation of membrane trafficking: Structural insights from a Rab/effector complex. Cell 1999, 96:755-758.
45. Iezzi M, Escher G, Meda P, Charollais A, Baldini G, Darchen F, Wollheim CB, Regazzi R: Subcellular distribution and function of Rab3A, B, C, and D isoforms in insulin-secreting cells. Mol Endocrinol 1999, 13:202-212.
46. Press B, Feng Y, Hoflack B, Wandinger-Ness A: Mutant Rab7 causes the accumulation of cathepsin D and cation- Independent mannose 6-phosphate receptor in an early endocytic compartment. J Cell Biol 1998, 140:1075-1089.
47. Ren M, Xu G, Zeng J, De Lemos-Chiarandini C, Adesnik M, Sabatini DD: Hydrolysis of GTP on Rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes. Proc Natl Acad Sci USA 1998, 95:6187-6192.
48. Chen W, Feng Y, Chen D, Wandinger-Ness A: Rab11 is required for trans-Golgi network-to-plasma membrane transport and a preferential target for GDP dissociation inhibitor. Mol Biol Cell 1998, 9:3241-3257.
49. Zacchi P, Stenmark H, Parton RG, Orioli D, Lim F, Giner A, Mellman I, Zerial M, Murphy C: Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells. J Cell Biol 1998, 140:1039-1053.
50. Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE, Altschuler Y, Ray GS, Goldenring JR: Association of Rab25 and Rab11A with the apical recycling system of polarized Madin- Darby canine kidney cells. Mol Biol Cell 1999, 10:47-61.
51. Barbieri MA, Hoffenberg S, Roberts R, Mukhopadhyay A, Pomrehn A, Dickey BF, Stahl PD: Evidence for a symmetrical requirement for Rab5-Gtp in in vitro endosome-endosome fusion. J Biol Chem 1998, 273:25850-25855.
52. Jones S, Richardson CJ, Litt RJ, Segev N: Identification of regulators for Ypt1 gtpase nucleotide cycling. Mol Biol Cell 1998, 9:2819-2837.
53. Vollmer P, Will E, Scheglmann D, Strom M, Gallwitz D: Primary structure and biochemical characterization of yeast GTPase- Activating proteins with substrate preference for the transport gtpase Ypt7p. Eur J Biochem 1999, 260:284-290.
54. Du LL, Collins RN, Novick PJ: Identification of a Sec4p GTPase- Activating protein (GAP) as a novel member of a Rab GAP family. J Biol Chem 1998, 273:3253-3256.
55. Nagano F, Sasaki T, Fukui K, Asakura T, Imazumi K, Takai Y: Molecular cloning and characterization of the noncatalytic subunit of the Rab3 subfamily-specific GTPase-activating protein. J Biol Chem 1998, 273:24781-24785.
56. Cuif MH, Possmayer F, Zander H, Bordes N, Jollivet F, Couedel Courteille A, Janoueix-Lerosey I, Langsley G, Bornens M, Goud B: Characterization of GAPCenA, a GTPase activating protein for Rab6, part of which associates with the centrosome. EMBO J 1999, 18:1772-1782. The authors have identified a new protein termed GAPCenA that acts as a GAP (GTPase activating protein) for Rab6. A minor pool of GAPCenA is associated with the centrosome, and forms complexes with cytosolic γ-tubulin, a protein involved in microtubule nucleation. This suggests that RabGAPs (which share homology domains with mitotic checkpoint proteins, see also [16•]) might be involved in the co-ordination of microtubule and membrane dynamics during mitosis.
57. Wu SK, Luan P, Matteson J, Zeng K, Nishimura N, Balch WE: Molecular role for the Rab binding platform of guanine nucleotide dissociation inhibitor in endoplasmic reticulum to Golgi transport J Biol Chem 1998, 273:26931-26938.
58. Anant JS, Desnoyers L, Machius M, Demeler B, Hansen JC, Westover KD, Deisenhofer J, Seabra MC: Mechanism of Rab geranylgeranylation: Formation of the catalytic ternary complex. Biochemistry 1998, 37:12559-12568.
59. Yang X, Matern HT, Gallwitz D: Specific binding to a novel and essential Golgi membrane protein (Yip1p) functionally links the transport GTPases Ypt1p and Ypt31p. EMBO J 1998, 17:4954-4963. The authors have identified a new Golgi-associated integral membrane protein termed Yip1p, which binds to Ypt1p and Ypt31p. They provide evidence that Yip1p might serve to recruit Ypt1p and Ypt31p onto Golgi membranes.
60. Rybin V, Ullrich O, Rubino M, Alexandrov K, Simon I, Seabra C, Goody R, Zerial M: GTPase activity of Rab5 acts as a timer for endocytic membrane fusion. Nature 1996, 383:266-269.
61. Richardson CJ, Jones S, Litt RJ, Segev N: GTP hydrolysis is not important for Ypt1 GTPase function in vesicular transport. Mol Cell Biol 1998, 18:827-838.
62. Marzesco AM, Galli T, Louvard D, Zahraoui A: The rod cGmp phosphodiesterase delta subunit dissociates the small gtpase Rab13 from membranes. J Biol Chem 1998, 273:22340-22345.
63. Bourne HR: Do GTPases direct membrane traffic in secretion? Cell 1988, 53:669-671.
64. Cao X, Ballew N, Barlowe C: Initial docking of ER-derived vesicles requires Uso1p and Ypt1p but is independent of SNARE proteins. EMBO J 1998, 17:2156-2165. In an assay that reconstitutes ER-to-Golgi transport in yeast, the authors have investigated the role of Ypt1p. GDI inhibits vesicle docking but not fusion of ER-derived vesicles with Golgi membranes. They also provide evidence that the SNARE proteins Sed5p, Bet1p and Bos1p are not required for the initial docking of vesicles. This study points to a role for Rab proteins in SNARE-independent docking/tethering of vesicles with target membranes (see also Ungermann et al. [66•]).
65. Sato K, Wickner W: Functional reconstitution of Ypt7p GTPase and a purified vacuole SNARE complex. Science 1998, 281:700-702.
66. Ungermann C, Sato K, Wickner W: Defining the functions of trans SNARE pairs. Nature 1998, 396:543-548. The authors have dissected the steps that lead to vacuole - vacuole fusion in vitro. They define a reversible Ypt7p-dependent 'tethering' step that precedes irreversible SNARE pairing.
67. Sacher M, Jiang Y, Barrowman J, Scarpa A, Burston J, Zhang L, Schieltz D, Yates JR III, Abeliovich H, Ferro-Novick S: TRAPP, a highly conserved novel complex on the cis-Golgi that mediates vesicle docking and fusion. EMBO J 1998, 17:2494-2503.
68. Guo W, Roth D, Walch-Solimena C, Novick P: The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J 1999, 18:1071-1080. The authors show that Sec15p, a component of the exocyst, associates with post-Golgi vesicles and binds to GTP-bound Sec4p. They also provide evidence that Sec4p is directly involved in the assembly of the exocyst proteins and in its binding to Sec3p, which marks specific sites of exocytosis at the plasma membrane.
69. Hsu SC, Hazuka CD, Foletti DL, Scheller RH: Targeting vesicles to specific sites on the plasma membrane: The role of the Sec6/8 complex. Trends Biochem Sci 1999, 9:150-153.
70. Echard A, Jollivet F, Martinez O, Lacapere JJ, Rousselet A, Janoueix Lerosey I, Goud B: Interaction of a Golgi-associated kinesin-like protein with rab6. Science 1998, 279:580-585. The authors have identified a new Golgi-associated kinesin-like protein termed Rabkinesin-6 as an effector of Rab6. This result provides the first direct evidence that one Rab function might be to regulate the movement of transport vesicles along the cytoskeleton.
71. Christoforidis S, McBride HM, Burgoyne RD, Zerial M: The Rab5 effector EEA1 is a core component of endosome docking. Nature 1999, 397:621-625. The authors have determined the minimal machinery needed for in vitro endosome-endosome fusion. EEA1 alone (or at least a fractionated cytosolic fraction highly enriched in this protein) can drive the fusion reaction, suggesting that EEA1 is an integral component of the docking and fusion machinery. The other putative Rab5 effectors might serve to regulate EEA1 activity.
72. 3 on endosomal membranes. As PI3-kinase activity is required for endosome fusion, this result provides the first molecular link between PI3-kinase and Rab5 in the regulation of endocytic membrane traffic.
73. Peterson MR, Burd CG, Emr SD: Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. Curr Biol 1999, 9:159-162. The authors show that Vac1p, a yeast endosomal protein closely related to EEA1, might function as a downstream effector of Vps21p, a RabGTPase that functions in Golgi-to-endosome transport. Vac1p directly interacts with Vps45p, a Sec1p homologue.
74. Zeng J, Ren M, Gravotta D, De Lemos-Chiarandini C, Lui M, Erdjument-Bromage H, Tempst P, Xu G, Shen TH, Morimoto T et al.: Identification of a putative effector protein for Rab11 that participates in transferrin recycling. Proc Natl Acad Sci USA 1999, 96:2840-2845.
75. Ostermeier C, Brunger AT: Structural basis of Rab effector specificity: Crystal structure of the small G protein Rab3a complexed with the effector domain of rabphilin-3A. Cell 1999, 96:363-374. The authors present the first crystal structure (2.6 Å resolution) of a Rab (Rab3A) in complex with an effector (Rabphilin-A). The crystal has been obtained with the GTPase mutant of Rab3A (Rab3 Glu81→Leu), with a few amino acids at the amino and carboxyl terminus deleted (leaving amino acids 19-217), and residues 40-170 of Rabphilin-A. The Rab3A interface with Rabphilin-A involves the switch I and switch II regions of Rab3A and three domains termed RabCDR. These domains are hypervariable among the Rab family and could enable Rab proteins to interact with a wide variety of effectors.
76. McLauchlan H, Newell J, Morrice N, Osborne A, West M, Smythe E: A novel role for Rab5-GDI in ligand sequestration into clathrin- coated pits. Curr Biol 1998, 8:34-45.
77. Imamura H, Takaishi K, Nakano K, Kodama A, Oishi H, Shiozaki H, Monden M, Sasaki T, Takai Y: Rho and Rab small G proteins coordinately reorganize stress fibers and focal adhesions in MDCK cells. Mol Biol Cell 1998, 9:2561-2575.