Drug targeting: Learning from toxin entry and trafficking in mammalian cells

Current Opinion in Drug Discovery and Development

Volumn 13, Issue 1, 2010, Pages 86-95

  Spooner, Robert A ^a   Watson, Peter ^b  

^a UNIVERSITY OF WARWICK   (United Kingdom)

^b CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Drug delivery; Drug targeting; Membrane transport; Toxin; Trafficking

Indexed keywords

IMMUNOTOXIN; NANOPARTICLE; TOXIN;

CELL MEMBRANE; CELL TRANSPORT; CYTOSOL; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG TARGETING; DRUG TRAFFIC; ENDOPLASMIC RETICULUM; MAMMAL CELL; MEMBRANE TRANSPORT; NONHUMAN; REVIEW;

ANIMALS; CELLS; DRUG DELIVERY SYSTEMS; ENDOPLASMIC RETICULUM; HUMANS; MODELS, BIOLOGICAL; NANOPARTICLES; PLASMA; PROTEIN TRANSPORT; SMALL MOLECULE LIBRARIES; TOXINS, BIOLOGICAL;

EID: 73849122818     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (95)

1. Jones AT: Intracellular drug delivery. Workshop report from the 28th International Symposium on Controlled Release of Bioactive Materials, San Diego, 23-24 June, 2001. Traffic (2001) 2(12):917-920.
2. Jones AT: Gateways and tools for drug delivery: Endocytic pathways and the cellular dynamics of cell penetrating peptides. Int J Pharm (2008) 354(1-2):34-38.
3. Deli MA: Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery. Biochim Biophys Acta (2009) 1788(4):892-910.
4. Guttman JA, Finlay BB: Tight junctions as targets of infectious agents. Biochim Biophys Acta (2009) 1788(4):832-841.
5. Takahashi A, Kondoh M, Masuyama A, Fujii M, Mizuguchi H, Horiguchi Y, Watanabe Y: Role of C-terminal regions of the C-terminal fragment of Clostridium perfringens enterotoxin in its interaction with claudin-4. J Control Release (2005) 108(1): 56-62. (Pubitemid 41476674)
6. Van Itallie CM, Betts L, Smedley JG 3rd, McClane BA, Anderson JM: Structure of the claudin-binding domain of Clostridium perfringens enterotoxin. J Biol Chem (2008) 283(1):268-274.
7. Fasano A, Fiorentini C, Donelli G, Uzzau S, Kaper JB, Margaretten K, Ding X, Guandalini S, Comstock L, Goldblum SE: Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest (1995) 96(2):710-720.
8. Wang W, Uzzau S, Goldblum SE, Fasano A: Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci (2000) 113(Pt 24):4435-4440.
9. Gopalakrishnan S, Pandey N, Tamiz AP, Vere J, Carrasco R, Somerville R, Tripathi A, Ginski M, Paterson BM, Alkan SS: Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator and absorption enhancer. Int J Pharm (2009) 365(1-2): 121-130.
10. Song KH, Fasano A, Eddington ND: Effect of the six-mer synthetic peptide (AT1002) fragment of zonula occludens toxin on the intestinal absorption of cyclosporin A. Int J Pharm (2008) 351(1-2):8-14.
11. Bulaj G: Integrating the discovery pipeline for novel compounds targeting ion channels. Curr Opin Chem Biol (2008) 12(4): 441-447.
12. Mueller M, Grauschopf U, Maier T, Glockshuber R, Ban N: The structure of a cytolytic ?-helical toxin pore reveals its assembly mechanism. Nature (2009) 459(7247):726-730.
13. Bourdeau RW, Malito E, Chenal A, Bishop BL, Musch MW, Villereal ML, Chang EB, Mosser EM, Rest RF, Tang WJ: Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis. J Biol Chem (2009) 284(21):14645-14656.
14. Giddings KS, Zhao J, Sims PJ, Tweten RK: Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin. Nat Struct Mol Biol (2004) 11(12):1173-1178.
15. Polekhina G, Giddings KS, Tweten RK, Parker MW: Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin. Proc Natl Acad Sci USA (2005) 102(3):600-605.
16. Bolitho P, Street SE, Westwood JA, Edelmann W, Macgregor D, Waring P, Murray WK, Godfrey DI, Trapani JA, Johnstone RW, Smyth MJ: Perforin-mediated suppression of B-cell lymphoma. Proc Natl Acad Sci USA (2009) 106(8):2723-2728.
17. Lena G, Trapani JA, Sutton VR, Ciccone A, Browne KA, Smyth MJ, Denny WA, Spicer JA: Dihydrofuro[3,4-c]pyridinones as inhibitors of the cytolytic effects of the pore-forming glycoprotein perforin. J Med Chem (2008) 51(23):7614-7624.
18. Kafsack BF, Pena JD, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB: Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science (2009) 323(5913):530-533.
19. Soletti RC, de Faria GP, Vernal J, Terenzi H, Anderluh G, Borges HL, Moura-Neto V, Gabilan NH: Potentiation of anticancer-drug cytotoxicity by sea anemone pore-forming proteins in human glioblastoma cells. Anticancer Drugs (2008) 19(5):517-525.
20. Lavie Y, Liscovitch M: Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences. Glycoconj J (2000) 17(3-4):253-259.
21. Bayley H: Membrane-protein structure: Piercing insights. Nature (2009) 459(7247):651-652.
22. van der Goot G, Young JA: Receptors of anthrax toxin and cell entry. Mol Aspects Med (2009) 30(6):406-412.
23. Watson P, Spooner RA: Toxin entry and trafficking in mammalian cells. Adv Drug Deliv Rev (2006) 58(15):1581-1596.
24. Paton AW, Beddoe T, Thorpe CM, Whisstock JC, Wilce MC, Rossjohn J, Talbot UM, Paton JC: AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature (2006) 443(7111):548-552.
25. Windschiegl B, Orth A, Römer W, Berland L, Stechmann B, Bassereau P, Johannes L, Steinem C: Lipid reorganization induced by Shiga toxin clustering on planar membranes. PLoS One (2009) 4(7):e6238.
26. Römer W, Berland L, Chambon V, Gaus K, Windschiegl B, Tenza D, Aly MR, Fraisier V, Florent JC, Perrais D, Lamaze C et al: Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature (2007) 450(7170):670-675.
27. Lauvrak SU, Wälchli S, Iversen TG, Slagsvold HH, Torgersen ML, Spilsberg B, Sandvig K: Shiga toxin regulates its entry in a Sykdependent manner. Mol Biol Cell (2006) 17(3):1096-1099.
28. Fuchs E, Haas AK, Spooner RA, Yoshimura S, Lord JM, Barr FA: Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. J Cell Biol (2007) 177(6):1133-1143.
29. van Deurs B, Sandvig K, Petersen OW, Olsnes S, Simons K, Griffiths G: Estimation of the amount of internalized ricin that reaches the trans-Golgi network. J Cell Biol (1988) 106(2):253-267.
30. Arighi CN, Hartnell LM, Aguilar RC, Haft CR, Bonifacino JS: Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J Cell Biol (2004) 165(1):123-133.
31. Bonifacino JS, Hurley JH: Retromer. Curr Opin Cell Biol (2008) 20(4):427-436.
32. Skånland SS, Wälchli S, Utskarpen A, Wandinger-Ness A, Sandvig K: Phosphoinositide-regulated retrograde transport of ricin: Crosstalk between hVps34 and sorting nexins. Traffic (2007) 8(3):297-309.
33. Bujny MV, Popoff V, Johannes L, Cullen PJ: The retromer component sorting nexin-1 is required for efficient retrograde transport of Shiga toxin from early endosome to the trans Golgi network. J Cell Sci (2007) 120(Pt 12):2010-2021.
34. Popoff V, Mardones GA, Tenza D, Rojas R, Lamaze C, Bonifacino JS, Raposo G, Johannes L: The retromer complex and clathrin define an early endosomal retrograde exit site. J Cell Sci (2007) 120(Pt 12):2022-2031.
35. Smith RD, Willett R, Kudlyk T, Pokrovskaya I, Paton AW, Paton JC, Lupashin VV: The COG complex, Rab6 and COPI define a novel Golgi retrograde trafficking pathway that is exploited by SubAB toxin. Traffic (2009) 10(10):1502-1517.
36. Lombardi D, Soldati T, Riederer MA, Goda Y, Zerial M, Pfeffer SR: Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J (1993) 12(2):677-682.
37. Smith DC, Spooner RA, Watson PD, Murray JL, Hodge TW, Amessou M, Johannes L, Lord JM, Roberts LM: Internalized Pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum. Traffic (2006) 7(4):379-393.
38. Amessou M, Fradagrada A, Falguières T, Lord JM, Smith DC, Roberts LM, Lamaze C, Johannes L: Syntaxin 16 and syntaxin 5 are required for efficient retrograde transport of several exogenous and endogenous cargo proteins. J Cell Sci (2007) 120(Pt 8):1457-1468.
39. Spooner RA, Watson P, Smith DC, Boal F, Amessou M, Johannes L, Clarkson GJ, Lord JM, Stephens DJ, Roberts LM: The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network. Biochem J (2008) 414(3):471-484.
40. White J, Johannes L, Mallard F, Girod A, Grill S, Reinsch S, Keller P, Tzschaschel B, Echard A, Goud B, Stelzer EH: Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells. J Cell Biol (1999) 147(4):743-760.
41. McKenzie J, Johannes L, Taguchi T, Sheff D: Passage through the Golgi is necessary for Shiga toxin B subunit to reach the endoplasmic reticulum. FEBS J (2009) 276(6):1581-1595.
42. Morlon-Guyot J, Méré J, Bonhoure A, Beaumelle B: Processing of Pseudomonas aeruginosa exotoxin A is dispensable for cell intoxication. Infect Immun (2009) 77(7):3090-3099.
43. Zolov SN, Lupashin VV: Cog3p depletion blocks vesicle-mediated Golgi retrograde trafficking in HeLa cells. J Cell Biol (2005) 168(5):747-759.
44. Shestakova A, Zolov S, Lupashin V: COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation. Traffic (2006) 7(2):191-204.
45. Rapak A, Falnes PO, Olsnes S: Retrograde transport of mutant ricin to the endoplasmic reticulum with subsequent translocation to cytosol. Proc Natl Acad Sci USA (1997) 94(8): 3783-3788.
46. Miesenböck G, Rothman JE: The capacity to retrieve escaped ER proteins extends to the trans-most cisterna of the Golgi stack. J Cell Biol (1995) 129(2):309-319.
47. Mallard F, Antony C, Tenza D, Salamero J, Goud B, Johannes L: Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of Shiga toxin B-fragment transport. J Cell Biol (1998) 143(4):973-990.
48. Girod A, Storrie B, Simpson JC, Johannes L, Goud B, Roberts LM, Lord JM, Nilsson T, Pepperkok R: Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum. Nat Cell Biol (1999) 1(7):423-430.
49. Chen A, AbuJarour RJ, Draper RK: Evidence that the transport of ricin to the cytoplasm is independent of both Rab6A and COPI. J Cell Sci (2003) 116(Pt 17):3503-3510.
50. Simpson JC, Dascher C, Roberts LM, Lord JM, Balch WE: Ricin cytotoxicity is sensitive to recycling between the endoplasmic reticulum and the Golgi complex. J Biol Chem (1995) 270(34):20078-20083.
51. Day PJ, Owens SR, Wesche J, Olsnes S, Roberts LM, Lord JM: An interaction between ricin and calreticulin that may have implications for toxin trafficking. J Biol Chem (2001) 276(10):7202-7208.
52. Spooner RA, Watson PD, Marsden CJ, Smith DC, Moore KA, Cook JP, Lord JM, Roberts LM: Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. Biochem J (2004) 383(Pt 2):285-293.
53. Majoul I, Ferrari D, Söling HD: Reduction of protein disulfide bonds in an oxidizing environment. The disulfide bridge of cholera toxin A-subunit is reduced in the endoplasmic reticulum. FEBS Lett (1997) 401(2-3):104-108.
54. Orlandi PA: Protein-disulfide isomerase-mediated reduction of the A subunit of cholera toxin in a human intestinal cell line. J Biol Chem (1997) 272(7):4591-4599.
55. McKee ML, FitzGerald DJ: Reduction of furin-nicked Pseudomonas exotoxin A: An unfolding story. Biochemistry (1999) 38(50): 16507-16513.
56. Vembar SS, Brodsky JL: One step at a time: Endoplasmic reticulum-associated degradation. Nat Rev Mol Cell Biol (2008) 9(12):944-957.
57. Teter K, Holmes RK: Inhibition of endoplasmic reticulumassociated degradation in CHO cells resistant to cholera toxin, Pseudomonas aeruginosa exotoxin A, and ricin. Infect Immun (2002) 70(11):6172-6179.
58. Tsai B, Rodighiero C, Lencer WI, Rapoport TA: Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell (2001) 104(6):937-948.
59. Pande AH, Scaglione P, Taylor M, Nemec KN, Tuthill S, Moe D, Holmes RK, Tatulian SA, Teter K: Conformational instability of the cholera toxin A1 polypeptide. J Mol Biol (2007) 374(4):1114-1128.
60. Mayerhofer PU, Cook JP, Wahlman J, Pinheiro TT, Moore KA, Lord JM, Johnson AE, Roberts LM: Ricin A chain insertion into endoplasmic reticulum membranes is triggered by a temperature increase to 37°C. J Biol Chem (2009) 284(15):10232-10242.
61. Falguières T, Johannes L: Shiga toxin B-subunit binds to the chaperone BiP and the nucleolar protein B23. Biol Cell (2006) 98(2):125-134.
62. Yu M, Haslam DB: Shiga toxin is transported from the endoplasmic reticulum following interaction with the luminal chaperone HEDJ/ERdj3. Infect Immun (2005) 73(4):2524-2532.
63. Spooner RA, Hart PJ, Cook JP, Pietroni P, Rogon C, Höhfeld J, Roberts LM, Lord JM: Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum. Proc Natl Acad Sci USA (2008) 105(45):17408-17413.
64. Slominska-Wojewodzka M, Gregers TF, Wälchli S, Sandvig K: EDEM is involved in retrotranslocation of ricin from the endoplasmic reticulum to the cytosol. Mol Biol Cell (2006) 17(4):1664-1675.
65. Wesche J, Rapak A, Olsnes S: Dependence of ricin toxicity on translocation of the toxin A-chain from the endoplasmic reticulum to the cytosol. J Biol Chem (1999) 274(48):34443-34449.
66. Bernardi KM, Forster ML, Lencer WI, Tsai B: Derlin-1 facilitates the retro-translocation of cholera toxin. Mol Biol Cell (2008) 19(3):877-884.
67. Koopmann JO, Albring J, Hüter E, Bulbuc N, Spee P, Neefjes J, Hämmerling GJ, Momburg F: Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Sec61p channel. Immunity (2000) 13(1):117-127.
68. Hazes B, Read RJ: Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry (1997) 36(37):11051-11054.
69. Deeks ED, Cook JP, Day PJ, Smith DC, Roberts LM, Lord JM: The low lysine content of ricin A chain reduces the risk of proteolytic degradation after translocation from the endoplasmic reticulum to the cytosol. Biochemistry (2002) 41(10):3405-3413.
70. Rodighiero C, Tsai B, Rapoport TA, Lencer WI: Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation. EMBO Rep (2002) 3(12):1222-1227.
71. Ampapathi RS, Creath AL, Lou DI, Craft JW Jr, Blanke SR, Legge GB: Order-disorder-order transitions mediate the activation of cholera toxin. J Mol Biol (2008) 377(3):748-760.
72. Argent RH, Parrott AM, Day PJ, Roberts LM, Stockley PG, Lord JM, Radford SE: Ribosome-mediated folding of partially unfolded ricin A-chain. J Biol Chem (2000) 275(13):9263-9269.
73. Zhang F, Sun S, Feng D, Zhao WL, Sui SF: A novel strategy for the invasive toxin: Hijacking exosome-mediated intercellular trafficking. Traffic (2009) 10(4):411-424.
74. Schorey JS, Bhatnagar S: Exosome function: From tumor immunology to pathogen biology. Traffic (2008) 9(6):871-881.
75. Zhao WL, Zhang F, Feng D, Wu J, Chen S, Sui SF: A novel sorting strategy of trichosanthin for hijacking human immunodeficiency virus type 1. Biochem Biophys Res Commun (2009) 384(3):347-351.
76. Brügger B, Glass B, Haberkant P, Leibrecht I, Wieland FT, Kräusslich HG: The HIV lipidome: A raft with an unusual composition. Proc Natl Acad Sci USA (2006) 103(8):2641-2646.
77. Kreitman RJ: Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies. BioDrugs (2009) 23(1):1-13.
78. Steinfeld SD, Youinou P: Epratuzumab (humanised anti-CD22 antibody) in autoimmune diseases. Expert Opin Biol Ther (2006) 6(9):943-949.
79. Kreitman RJ, Wilson WH, Bergeron K, Raggio M, Stetler- Stevenson M, FitzGerald DJ, Pastan I: Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N Engl J Med (2001) 345(4):241-247.
80. Alderson RF, Kreitman RJ, Chen T, Yeung P, Herbst R, Fox JA, Pastan I: CAT-8015: A second-generation pseudomonas exotoxin A-based immunotherapy targeting CD22-expressing hematologic malignancies. Clin Cancer Res (2009) 15(3):832-839.
81. Mathew M, Verma RS: Humanized immunotoxins: A new generation of immunotoxins for targeted cancer therapy. Cancer Sci (2009) 100(8):1359-1365.
82. Tejuca M, Anderluh G, Dalla Serra M: Sea anemone cytolysins as toxic components of immunotoxins. Toxicon (2009) 54(8): 1206-1214.
83. Wan L, Zeng L, Chen L, Huang Q, Li S, Lu Y, Li Y, Cheng J, Lu X: Expression, purification, and refolding of a novel immunotoxin containing humanized single-chain fragment variable antibody against CTLA4 and the N-terminal fragment of human perforin. Protein Expr Purif (2006) 48(2):307-313.
84. Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ: Immunotoxin treatment of cancer. Annu Rev Med (2007) 58:221-237.
85. Okada H, Kohanbash G, Zhu X, Kastenhuber ER, Hoji A, Ueda R, Fujita M: Immunotherapeutic approaches for glioma. Crit Rev Immunol (2009) 29(1):1-42.
86. Spooner RA, Smith DC, Easton AJ, Roberts LM, Lord JM: Retrograde transport pathways utilised by viruses and protein toxins. Virol J (2006) 3:26.
87. Klausner RD, Donaldson JG, Lippincott-Schwartz J: Brefeldin A: Insights into the control of membrane traffic and organelle structure. J Cell Biol (1992) 116(5):1071-1080.
88. Feng Y, Jadhav AP, Rodighiero C, Fujinaga Y, Kirchhausen T, Lencer WI: Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic reticulum requires the trans- Golgi network but not the Golgi apparatus in Exo2-treated cells. EMBO Rep (2004) 5(6):596-601.
89. Sáenz JB, Doggett TA, Haslam DB: Identification and characterization of small molecules that inhibit intracellular toxin transport. Infect Immun (2007) 75(9):4552-4561.
90. Sáenz JB, Sun WJ, Chang JW, Li J, Bursulaya B, Gray NS, Haslam DB: Golgicide A reveals essential roles for GBF1 in Golgi assembly and function. Nat Chem Biol (2009) 5(3):157-165.
91. Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T: Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell (2006) 10(6):839-850.
92. Mignet N, Brun A, Degert C, Delord B, Roux D, Hélène C, Laversanne R, François JC: The spherulites: A promising carrier for oligonucleotide delivery. Nucleic Acids Res (2000) 28(16):3134-3142.
93. Poirier C, van Effenterre D, Delord B, Johannes L, Roux D: Specific adsorption of functionalized colloids at the surface of living cells: A quantitative kinetic analysis of the receptor-mediated binding. Biochim Biophys Acta (2008) 1778(10):2450-2457.
94. Bouter A, Delord B, Dransart E, Poirier C, Johannes L, van Effenterre D: Intracellular trafficking of Shiga-toxin-B-subunitfunctionalized spherulites. Biol Cell (2008) 100(12):717-725.
95. Tekle C, Deurs B, Sandvig K, Iversen TG Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands. Nano Lett (2008) 8(7):1858-1865.