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Protoplasma

, Volume 210, Issue 1–2, pp 1–10 | Cite as

Rab GTPases as regulators of transport through endosomes

  • Peter van der Sluijs
  • Lisya Gerez
Focus on Cellular Biochemistry

Summary

Early endocytic compartments are a highly dynamic, heterogeneous class of prelysosomal organelles that receive internalized proteins from the plasma membrane and sort these to various intracellular destinations. Several monomeric Rab GTPases are associated with the cytoplasmic surface of endosomes and regulate the dynamics of this endomembrane system. We discuss the endosomal Rab proteins and their effector proteins and how they might control vesicular transport through the endocytic pathway.

Keywords

Endocytosis Rab proteins Effectors 

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References

  1. Advani RJ, Bae HR, Bock JB, Chao DS, Doung YC, Prekeris R, Yoo JS, Scheller RH (1998) Seven novel mammalian SNARE proteins localize to distinct membrane compartments. J Biol Chem 273: 10317–10324Google Scholar
  2. Alexandrov K, Horiuchi H, Steele-Mortimer O, Seabra M, Zerial M (1994) Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes. EMBO J 13: 5262–5273Google Scholar
  3. Andres DA, Seabra M, Brown M, Armstrong SA, Smeland TE, Cremers FPM, Goldstein JL (1993) cDNA cloning of component A of rab geranylgeranyl transferase and demonstration of its role as a rab escort protein. Cell 73: 1091–1100Google Scholar
  4. Armstrong JA, Craighead MW, Watson R, Ponnambalam S, Bowden S (1993) S. pombe ypt5: a homologue of the rab5 endosome fusion regulator. Mol Biol Cell 4: 583–592Google Scholar
  5. Ayad N, Hull M, Mellman I (1997) Mitotic phosphorylation of rab4 prevents binding to a specific receptor on endosomes. EMBO J 16: 4497–4507Google Scholar
  6. Barbieri MA, Li G, Colombo MI, Stahl PD (1994) Rab5, an early acting endosomal GTPase supports in vitro endosome fusion without GTP hydrolysis. J Biol Chem 269: 18720–18722Google Scholar
  7. Benmerah A, Lamaze C, Begue B, Schmid SL, Dautry-Varsat A, Cerf-Bensussan N (1998) AP-2/Epsl5 interaction is required for receptor mediated endocytosis. J Cell Biol 140: 1055–1062Google Scholar
  8. Birky CW (1983) The partitioning of cytoplasmic organelles at cell division. Int Rev Cytol Suppl 15: 49–88Google Scholar
  9. Bottger G, Nagelkerken B, van der Sluijs P (1996) Rab4 and rab7 define distinct endocytic compartments. J Biol Chem 271: 29191–29197Google Scholar
  10. Brondyk WH, McKiernan CJ, Fortner KA, Stabila P, Holz RW, Macara IG (1995) Interaction cloning of rabin3, a novel protein that associates with the ras-like GTPase rab3A. Mol Cell Biol 15: 1137–1143Google Scholar
  11. Bucci C, Parton R, Mather I, Stunnenberg H, Simons K, Zerial M (1992) The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70: 715–728Google Scholar
  12. —, Wandinger-Ness A, Lütcke A, Chiarello M, Bruni CB, Zerial M (1994) Rab5a is a common component of the apical and basolateral endocytic machinery in polarized epithelial cells. Proc Natl Acad Sci USA 91: 5061–5065Google Scholar
  13. —, Lütcke A, Mortimer OS, Olkkonen VM, Dupree P, Chiariello M, Bruni CB, Simons K, Zerial M (1995) Co-operative regulation of endocytosis by three rab5 isoforms. FEBS Lett 366: 65–71Google Scholar
  14. Burd CG, Emr SD (1998) Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. Mol Cell 2: 157–162Google Scholar
  15. Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE, Altschuler Y, Ray GS, Goldenring JR (1999) Association of rab25 and rab11a with the apical recycling system of polarized MDCK cells. Mol Biol Cell 10: 47–61Google Scholar
  16. Chavrier P, Parton RG, Hauri HP, Simons K, Zerial M (1990) Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 62: 317–329Google Scholar
  17. Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P (1998) Epsin is an EH-domain-binding protein implicated in clathrin mediated endocytosis. Nature 394: 793–797Google Scholar
  18. —, Slepnev VI, De Fiore PP, De Camilli P (1999) The interaction of epsin and eps15 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation dependent dephosphorylation in nerve terminals. J Biol Chem 274: 3257–3260Google Scholar
  19. Chen W, Feng Y, Chen D, Wandinger-Ness A (1998) Rab11 is required for trans Golgi network to plasma membrane transport and a preferential target for GDP dissociation inhibitor. Mol Biol Cell 9: 3241–3257Google Scholar
  20. Coda L, Salcini E, Confalonieri S, Pelicci G, Sorkina T, Sorkin A, Pelicci PG, Di Fiore PP (1998) Eps15R is a tyrosine kinase substrate with characteristics of a docking protein possibly involved in coated pits mediated internalization. J Biol Chem 273: 3003–3012Google Scholar
  21. Cosulich SC, Horiuchi H, Zerial M, Clarke PR, Woodman PG (1997) Cleavage of rabaptin-5 blocks endosome fusion during apoptosis. EMBO J 16: 6182–6191Google Scholar
  22. Damke H, Baba T, Warnock D, Schmid SL (1994) Induction of mutant dynamin specifically blocks endocytic coated vesicle formation. J Cell Biol 127: 915–924Google Scholar
  23. Daro E, van der Sluijs P, Galli T, Mellman I (1996) Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling. Proc Natl Acad Sci USA 93: 9559–9564Google Scholar
  24. David C, McPherson P, Mundingl O, De Camilli P (1996) A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc Natl Acad Sci USA 93: 331–335Google Scholar
  25. de Hoop M, Huber LA, Stenmark H, Williamson E, Zerial M, Parton RG, Dotti CG (1994) The involvement of the small GTP-binding protein rab5a in neuronal endocytosis. Neuron 13: 11–22Google Scholar
  26. Diaz E, Schimmoller F, Pfeffer SR (1997) A novel rab9 effector required for endosome to TGN transport. J Cell Biol 138: 283–290Google Scholar
  27. Dirac-Svejstrup AB, Sumizawa T, Pfeffer SR (1997) Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI. EMBO J 16: 465–472Google Scholar
  28. Dotti CG, Simons K (1990) Polarized sorting of viral glycoproteins to the axonal and dendrites of hippocampal neurons in culture. Cell 62: 63–72Google Scholar
  29. Felder S, Miller K, Moehren G, Ullrich A, Schlessinger J, Hopkins CR (1990) Kinase activity controls the sorting of the epidermal growth factor within the multivesicular body. Cell 61: 623–634Google Scholar
  30. Feng Y, Press B, Wandinger Ness A (1995) Rab7: an important regulator of late endocytic membrane traffic. J Cell Biol 131: 1435–1452Google Scholar
  31. Fernandez-Borja M, Wubbolts R, Calafat J, Janssen H, Divecha N, Dusseljee S, Neefjes J (1999) Multivesicular body morphogenesis requires phosphatidyl-inositol 3-kinase activity. Curr Biol 9: 55–58Google Scholar
  32. Galli T, Chilcote T, Mundigl O, Binz T, Niemann H, De Camilli P (1994) Tetanus toxin mediated cleavage of cellubrevin impairs exocytosis of transferrin receptor containing vesicles in CHO cells. J Cell Biol 125: 1015–1024Google Scholar
  33. Gaullier JM, Simonsen A, D'Arrigo A, Bremnes B, Stenmark H, Aasland R (1998) FYVE fingers bind PtdIns(3)P. Nature 394: 432–433Google Scholar
  34. Ghosh RN, Mallet WG, Soe TT, McGraw TE, Maxfield FR (1998) An endocytosed TGN38 chimeric protein is delivered to the TGN after trafficking through the endocytic recycling compartment in CHO cells. J Cell Biol 142: 923–936Google Scholar
  35. Gorvel JP, Chavrier P, Zerial M, Gruenberg J (1991) Rab5 controls early endosome fusion in vitro. Cell 64: 915–925Google Scholar
  36. Gournier H, Stenmark H, Rybin V, Lippe R, Zerial M (1998) Two distinct effectors of the small GTPase rab5 cooperate in endocytic membrane fusion. EMBO J 17: 1930–1940Google Scholar
  37. Herskovits JS, Burgess CC, Obar RA, Vallee RB (1993) Effects of mutant dynamin on endocytosis. J Cell Biol 122: 565–568Google Scholar
  38. Horazdovski BF, Busch GR, Emr S (1994) VPS21 encodes a rab5-like GTP binding protein that is required for the sorting of yeast vacuolar proteins. EMBO J 13: 1297–1309Google Scholar
  39. Horiuchi H, Lippe R, McBride HM, Rubino M, Woodman P, Stenmark H, Rybin V, Wilm M, Ashman K, Mann M, Zerial M (1997) A novel rab5 GDP/GTP exchange factor complexed to rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell 90: 1149–1159Google Scholar
  40. Hunziker W, Peters PJ (1998) Rab17 localizes to recycling endosomes and regulates receptor mediated transcytosis in epithelial cells. J Biol Chem 273: 15734–15741Google Scholar
  41. Kornfeld S, Mellman I (1989) The biogenesis of lysosomes. Annu Rev Cell Biol 5: 483–525Google Scholar
  42. Lazzarino DA. Blier P, Mellman I (1998) The monomeric guanosine triphosphatase rab4 controls an essential step on the pathway of receptor mediated antigen processing in B cells. J Exp Med 188: 1769–1774Google Scholar
  43. Lombardi D, Soldati T, Riederer M, Zerial M, Pfeffer S (1993) Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J 12: 677–682Google Scholar
  44. Lowe M, Nakamura N, Warren G (1998) Golgi division and membrane traffic. Trends Cell Biol 8: 40–44Google Scholar
  45. Lütcke A, Jansson S, Parton R, Chavrier P, Valencia A, Huber L, Lehtonen E, Zerial M (1993) Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization. J Cell Biol 121: 553–564Google Scholar
  46. Mallard F, Anthony C, Tenza D, Salamero J, Goud B, Johannes L (1998) Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of Shiga toxin B fragment transport. J Cell Biol 143: 973–990Google Scholar
  47. Mayor S, Presley J, Maxfield F (1993) Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process. J Cell Biol 121: 1257–1270Google Scholar
  48. McLaughlan H, Newell J, Morrice N. Osborne A, West M. Smythe E (1998) A novel role for rab-GDI in ligand sequestration into clathrin-coated pits. Curr Biol 8: 34–45Google Scholar
  49. McMahon HT, Ushkayov YA, Edelmann L, Link E, Binz T, Niemann H, Jahn R, Südhof TC (1993) Cellubrevin is a ubiquitous tetanus toxin substrate homologous to a putative synaptic vesicle fusion protein. Nature 364: 346–349Google Scholar
  50. Mellman I (1996) Endocytosis and molecular sorting. Annu Rev Cell Dev Biol 12: 575–626Google Scholar
  51. —, Simons K (1992) The golgi complex: in vitro veritas? Cell 68: 829–840Google Scholar
  52. Mills IG, Jones AT, Clague MJ (1998) Involvement of the endosomal autoantigen EEA1 in homotypic fusion of early endosomes. Curr Biol 8: 881–884Google Scholar
  53. Neve RL, Coopersmith R, McPhie DL, Santeufemio C, Pratt KG, Murphy CJ, Lynn SD (1998) The neuronal growth-associated protein GAP-43 interacts with rabaptin-5 and participates in endocytosis. J Neurosci 18: 7757–7767Google Scholar
  54. Odorizzi G, Babst M, Emr SD (1998) Fab1p PtdIns(3)P5-kinase function essential for protein sorting in the multivesicular body. Cell 95: 847–858Google Scholar
  55. Ohya T, Sasaki T, Kato M, Takai Y (1998) Involvement of rabphilin3 in endocytosis through interaction with rabaptin5. J Biol Chem 273: 613–617Google Scholar
  56. Olkkonen V, Stenmark H (1997) Role of rabGTPases in membrane traffic. Int Rev Cytol 126: 1–85Google Scholar
  57. Piper RC, Cooper AA, Yang H, Stevens TH (1995) VPS27 controls vacuolar and endocytic traffic through a prevacuolar compartment in Saccharomyces cerevisiae. J Cell Biol 131: 603–618Google Scholar
  58. Prekeris R, Klumperman J, Chen YA, Scheller RH (1998) Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes. J Cell Biol 143: 957–971Google Scholar
  59. Press B, Feng Y, Hoflack B, Wandinger-Ness A (1998) Mutant rab7 causes the accumulation of cathepsin D and cation independent mannose 6-phosphate receptor in an early endocytic compartment. J Cell Biol 140: 1075–1089Google Scholar
  60. Ren M, Zeng J, Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD (1996) In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase. Proc Natl Acad Sci USA 93: 5151–5155Google Scholar
  61. —, Xu G, Zeng J, Chiarandini CL, Adesnik M, Sabatini DD (1998) 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 recycling endosomes. Proc Natl Acad Sci USA 95: 6187–6192Google Scholar
  62. Riederer M, Soldati T, Shapiro AD, Lin J, Pfeffer SR (1994) Lysosome biogenesis requires rab9 function and receptor recycling from endosomes to the trans Golgi network. J Cell Biol 125: 573–582Google Scholar
  63. Rybin V, Ullrich O, Rubino M, Alexandrov K, Simon I, Seabra M, Goody R, Zerial M (1996) GTPase activity of rab5 acts as a timer for endocytic membrane fusion. Nature 383: 266–269Google Scholar
  64. Shen F, Seabra M (1996) Mechanism of digeranylgeranylation of rab proteins. J Biol Chem 271: 3692–3698Google Scholar
  65. Shibata H, Omata W, Suzuki Y, Tanaka S, Kojima I (1996) A synthetic peptide corresponding to the rab4 hypervariable carboxyterminal domain inhibits insulin action on glucose transport in rat adipocytes. J Biol Chem 271: 9704–9709Google Scholar
  66. Shima DT, Poch NC, Pepperkok R, Warren G (1998) An ordered inheritance strategy for the Golgi apparatus: visualization of mitotic disassembly reveals a role for the mitotic spindle. J Cell Biol 141: 955–966Google Scholar
  67. Shirataki H, Kaibuchi K, Sakodo T, Kishida S, Yamaguchi T, Wada K, Miyazaki M, Takai Y (1993) Rabphilin-3A, a putative target protein for smgp25A/rab3Ap25 small GTP binding protein related to synaptotagmin. Mol Cell Biol 13: 2061–2068Google Scholar
  68. Simonsen A, Lippe R, Christoforidis S, Gaullier JM, Brech A, Callaghan J, Toh BH, Murphy C, Zerial M, Stenmark H (1998) EEA1 links PI(3)K function to rab5 regulation of endosome fusion. Nature 394: 494–498Google Scholar
  69. Singer-Krüger SB, Stenmark H, Dusterhoft A, Philippsen P, Yoo JS, Gallwitz D, Zerial M (1994) Role of three rab5-like GTPases, Ypt51p, Ypt52p, and Ypt53p, in the endocytic and vacuolar protein sorting pathways of yeast. J Cell Biol 125: 283–298Google Scholar
  70. Stenmark H, Parton R, Steele-Mortimer O, Lutcke A, Gruenberg J, Zerial M (1994) Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J 13: 1287–1296Google Scholar
  71. —, Vitale G, Ullrich O, Zerial M (1995) Rabaptin-5 is a direct effector of the small GTPase rab5 in endocytic membrane fusion. Cell 83: 423–432Google Scholar
  72. —, Aasland R, Toh BH, D'Arrigo A (1996) Endosomal localization of the autoantigen EEA1 is mediated by a Zinc-binding FYVE finger. J Biol Chem 271: 24048–24054Google Scholar
  73. Tang BL, Tan AEH, Lim LK, Lee SS, Low DYH, Hong W (1998) Syntaxin 12, a member of the syntaxin family localized to the endosome. J Biol Chem 273: 6944–6950Google Scholar
  74. Teter K, Chandy G, Quinones B, Pereyra K, Machen T, Moore HPH (1998) Cellubrevin targeted fluorescence uncovers heterogeneity in the recycling endosomes. J Biol Chem 273: 19625–19633Google Scholar
  75. Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL (1998) SARA, a FYVE domain protein that recruits Smad2 to the TGF-β receptor. Cell 95: 779–791Google Scholar
  76. Ullrich O, Stenmark H, Alexandrov K, Huber L, Kaibuchi K, Sasaki T, Takai Y, Zerial M (1993) Rab GDI as a general regulator for the membrane association of rab proteins. J Biol Chem 268: 18143–18150Google Scholar
  77. —, Horiuchi H, Bucci C, Zerial M (1994) Membrane association of rab5 mediated by GDP-dissociation inhibitor and accompanied by GDP/GTP exchange. Nature 368: 157–160Google Scholar
  78. —, Reinsch O, Urbe S, Zerial M, Parton R (1996) Rab11 regulates recycling through the pericentriolar recycling endosome. J Cell Biol 135: 913–924Google Scholar
  79. Urbe S, Huber LA, Zerial M, Tooze SA, Parton RG (1993) Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC12 cells. FEBS Lett 334: 175–182Google Scholar
  80. Valentijn JA, Civita DQ, Gumkowski FD, Jamieson J (1997) Rab4 associates with the actin terminal web in developing rat pancreatic acinar cells. Eur J Cell Biol 72: 1–8Google Scholar
  81. Van Delft S, Schumacher C, Hage W, Verkleij AJ, Van Bergen en Henegouwen PMP (1997) Association and colocalization of eps15 with adaptor protein-2 and clathrin. J Cell Biol 136: 811–821Google Scholar
  82. van der Sluijs P, Hull M, Zahraoui A, Tavitian A, Goud B, Mellman I (1991) The small GTP binding protein rab4 is associated with early endosomes. Proc Natl Acad Sci USA 88: 6313–6317Google Scholar
  83. — —, Huber LA, Male P, Goud B, Mellman I (1992a) Reversible phosphorylation-dephosphorylation determines the localization of rab4 during the cell cycle. EMBO J 11: 4379–4389Google Scholar
  84. — —, Webster P, Goud B, Mellman I (1992b) The small GTP binding protein rab4 controls an early sorting event on the endocytic pathway. Cell 70: 729–740Google Scholar
  85. van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van der Ouweland A, Halley D, Young Burley J, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson R, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JBM, Ward S, Green AJ, Yates JRW, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ (1997) Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277: 805–808Google Scholar
  86. —, Nellist M, Nagelkerken B, Cheadle J, Snell R, van der Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P (1998) Interactions between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 7: 1053–1057Google Scholar
  87. Vitale G, Rybin V, Christoforidis S, Thornqvist PO, McCaffrey M, Stenmark H, Zerial M (1998) Distinct rab-binding domains mediate the interaction of rabaptin-5 with GTP-bound rab4 and rab5. EMBO J 17: 1941–1951Google Scholar
  88. Vollenweider P, Martin SS, Haruta T, Morris AJ, Nelson JG, Cormont M, Le Marchand Brustel Y, Rose DW, Olefsky JM (1997) The small GTP binding protein rab4 is involved in insulin induced GLUT4 translocation and actin filament rearangement in 3T3-L1 cells. Endocrinology 138: 4941–4949Google Scholar
  89. Wang Y, Okamoto M, Schmitz F, Hofman K, Südhof TC (1997) Rim is a putative rab3 effector in regulating synaptic vesicle fusion. Nature 388: 593–598Google Scholar
  90. Warren G (1993) Membrane partitioning during cell division. Annu Rev Biochem 62: 323–348Google Scholar
  91. —, Wickner W (1996) Organelle inheritance. Cell 84: 395–400Google Scholar
  92. Weisman LS, Wickner W (1992) Molecular characterization of VAC1, a gene required for vacuole inheritance and vacuole protein sorting. J Biol Chem 267: 618–623Google Scholar
  93. Wichmann H, Hengst L, Gallwitz D (1992) Endocytosis in yeast: evidence for the involvement of a small GTP binding protein (Ypt7p). Cell 71: 1131–1142Google Scholar
  94. Wilson AL, Erdman RA, Maltese WA (1996) Association of rab1b with GDI is required for recycling but not initial membrane targeting of the rab protein. J Biol Chem 271: 10932–10940Google Scholar
  95. Wong SH, Xu Y, Zhang T, Hong W (1998a) Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment. J Biol Chem 273: 375–380Google Scholar
  96. —, Zhang T, Xu Y, Subramaniam VN, Griffiths G, Hong W (1998b) Endobrevin, a novel synaptobrevin/VAMP-like protein preferentially associated with early endosome. Mol Biol Cell 9: 1549–1563Google Scholar
  97. Xiao GH, Shoarinejad F, Jin F, Golemis E, Yeung RS (1997) The tuberous sclerosis 2 gene product, tuberin, functions as a rab5 GTPase activating protein (GAP) in modulating endocytosis. J Biol Chem 272: 6097–6100Google Scholar
  98. Yamashiro DJ, Tycko B, Fluss SR, Maxfield FR (1984) Segregation of transferrin to a mildly acidic (pH 6.5) para-Golgi compartment in the recycling pathway. Cell 37: 789–800Google Scholar
  99. Yoshimori T, Keller P, Roth MG, Simons K (1996) Different biosynthetic transport routes to the plasma membrane in BHK and CHO cells. J Cell Biol 133: 247–256Google Scholar
  100. Zacchi P, Stenmark H, Parton RG, Orioli D, Lim F, Giner A, Zerial M, Murphy C (1998) Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells. J Cell Biol 140: 1039–1053Google Scholar

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • Peter van der Sluijs
    • 1
  • Lisya Gerez
    • 1
  1. 1.Department of Cell Biology, AZU Rm H02.314Utrecht University School of MedicineCX UtrechtThe Netherlands

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