Membrane translocation of diphtheria toxin fragment A exploits early to late endosome trafficking machinery

After reaching early endosomes by receptor‐mediated endocytosis, diphtheria toxin (DT) molecules have two possible fates. A large pool enters the degradative pathway whereas a few molecules become cytotoxic by translocating their catalytic fragment A (DTA) into the cytosol. Impairment of DT degradation by microtubule depolymerization does not block DT cytotoxicity. Therefore, DTA membrane translocation into the cytosol occurs from an endocytic compartment located upstream of late endosomes. Comparisons between early endosomes and endocytic carrier vesicles in a cell‐free translocation assay have demonstrated that early endosomes are the earliest endocytic compartment from which DTA translocates. DTA translocation is ATP‐dependent, requires early endosomal acidification, and is increased by the addition of cytosol. Cytosol‐dependent DTA translocation is GTPγS‐insensitive but is blocked by anti‐βCOP antibodies.

[1]  F. Gu,et al.  An endosomal beta COP is involved in the pH-dependent formation of transport vesicles destined for late endosomes , 1996, The Journal of cell biology.

[2]  C. Futter,et al.  Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes , 1996, The Journal of cell biology.

[3]  H. Geuze,et al.  A novel class of clathrin-coated vesicles budding from endosomes , 1996, The Journal of cell biology.

[4]  H. Geuze,et al.  Transport from late endosomes to lysosomes, but not sorting of integral membrane proteins in endosomes, depends on the vacuolar proton pump , 1995, The Journal of cell biology.

[5]  S. Olsnes,et al.  Induction of Toxin Sensitivity in Insect Cells by Infection with Baculovirus Encoding Diphtheria Toxin Receptor (*) , 1995, The Journal of Biological Chemistry.

[6]  F. Maxfield,et al.  Membrane transport in the endocytic pathway. , 1995, Current opinion in cell biology.

[7]  B. Almond,et al.  The cytoplasmic domain of the diphtheria toxin receptor (HB-EGF precursor) is not required for receptor-mediated endocytosis. , 1994, The Journal of biological chemistry.

[8]  D. Strickland,et al.  In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella , 1994, The Journal of cell biology.

[9]  M. J. Clague,et al.  Vacuolar ATPase activity is required for endosomal carrier vesicle formation. , 1994, The Journal of biological chemistry.

[10]  K. Mostov,et al.  Possible role of both the alpha and beta gamma subunits of the heterotrimeric G protein, Gs, in transcytosis of the polymeric immunoglobulin receptor. , 1993, The Journal of biological chemistry.

[11]  G. Griffiths,et al.  Cytoplasmic dynein-dependent vesicular transport from early to late endosomes [published erratum appears in J Cell Biol 1994 Feb;124(3):397] , 1993, The Journal of cell biology.

[12]  M. Zerial,et al.  Rab GTPases in vesicular transport. , 1993, Current opinion in cell biology.

[13]  R. Pepperkok,et al.  β-COP is essential for biosynthetic membrane transport from the endoplasmic reticulum to the Golgi complex in vivo , 1993, Cell.

[14]  C. Kocks,et al.  A chimeric toxin to study the role of the 21 kDa GTP binding protein rho in the control of actin microfilament assembly. , 1993, The EMBO journal.

[15]  M. Murgia,et al.  Cell penetration of diphtheria toxin. Reduction of the interchain disulfide bridge is the rate-limiting step of translocation in the cytosol. , 1993, The Journal of biological chemistry.

[16]  E. Ungewickell,et al.  Clathrin-associated proteins of bovine brain coated vesicles. An analysis of their number and assembly-promoting activity. , 1992, The Journal of biological chemistry.

[17]  D. Russell,et al.  Expression cloning of a diphtheria toxin receptor: Identity with a heparin-binding EGF-like growth factor precursor , 1992, Cell.

[18]  A. Bienvenüe,et al.  Selective translocation of the A chain of diphtheria toxin across the membrane of purified endosomes. , 1992, The Journal of biological chemistry.

[19]  Katherine A. Kantardjieff,et al.  The crystal structure of diphtheria toxin , 1992, Nature.

[20]  Y. Moriyama,et al.  Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. , 1991, The Journal of biological chemistry.

[21]  H. Geuze,et al.  Late endosomes derive from early endosomes by maturation , 1991, Cell.

[22]  M. Zerial,et al.  rab5 controls early endosome fusion in vitro , 1991, Cell.

[23]  E. Mekada,et al.  The cytotoxic action of diphtheria toxin and its degradation in intact Vero cells are inhibited by bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase. , 1990, The Journal of biological chemistry.

[24]  T. Schroer,et al.  Microtubule- and motor-dependent fusion in vitro between apical and basolateral endocytic vesicles from MDCK cells , 1990, Cell.

[25]  C. Hopkins,et al.  Movement of internalized ligand–receptor complexes along a continuous endosomal reticulum , 1990, Nature.

[26]  A. Ullrich,et al.  Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body , 1990, Cell.

[27]  F. Brodsky,et al.  100-kDa polypeptides in peripheral clathrin-coated vesicles are required for receptor-mediated endocytosis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[28]  K. Howell,et al.  Characterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro , 1989, The Journal of cell biology.

[29]  B. Rönnberg,et al.  Cellular regulation of diphtheria toxin cell surface receptors. , 1989, Toxicon : official journal of the International Society on Toxinology.

[30]  K. Howell,et al.  Membrane traffic in endocytosis: insights from cell-free assays. , 1989, Annual review of cell biology.

[31]  K. Altendorf,et al.  Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[32]  I. Mellman,et al.  The mannose 6-phosphate receptor and the biogenesis of lysosomes , 1988, Cell.

[33]  T. Strom,et al.  Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor- mediated action of a diphtheria toxin-related interleukin 2 fusion protein , 1988, The Journal of experimental medicine.

[34]  R. Collier,et al.  [31] Diphtheria toxin: Quantification and assay , 1988 .

[35]  R. Collier,et al.  Diphtheria toxin: quantification and assay. , 1988, Methods in enzymology.

[36]  K. Sandvig,et al.  Cell-mediated reduction of the interfragment disulfide in nicked diphtheria toxin. A new system to study toxin entry at low pH. , 1987, The Journal of biological chemistry.

[37]  R. Collier,et al.  Expression of a mutant, full-length form of diphtheria toxin in Escherichia coli , 1987, Infection and immunity.

[38]  M. Robinson.  100-kD coated vesicle proteins: molecular heterogeneity and intracellular distribution studied with monoclonal antibodies , 1987, The Journal of cell biology.

[39]  T. Kreis,et al.  A microtubule-binding protein associated with membranes of the Golgi apparatus , 1986, The Journal of cell biology.

[40]  G K Lewis,et al.  Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product , 1985, Molecular and cellular biology.

[41]  P. Bonventre,et al.  Receptor-mediated entry of diphtheria toxin into monkey kidney (Vero) cells: electron microscopic evaluation , 1985, Infection and immunity.

[42]  B. Goud,et al.  Inhibition of coated pit formation in Hep2 cells blocks the cytotoxicity of diphtheria toxin but not that of ricin toxin , 1985, The Journal of cell biology.

[43]  M. Brown,et al.  Visualization of acidic organelles in intact cells by electron microscopy. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[45]  R D Klausner,et al.  Receptor-mediated endocytosis of transferrin in K562 cells. , 1983, The Journal of biological chemistry.

[46]  J. Putney.  Cellular regulation. , 1982, Science.

[47]  W. N. Burnette,et al.  "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. , 1981, Analytical biochemistry.

[48]  M. Simon,et al.  The entry of diphtheria toxin into the mammalian cell cytoplasm: evidence for lysosomal involvement , 1980, The Journal of cell biology.

[49]  K. Sandvig,et al.  Diphtheria toxin entry into cells is facilitated by low pH , 1980, The Journal of cell biology.

[50]  P. Boquet,et al.  Binding of triton X-100 to diphtheria toxin, crossreacting material 45, and their fragments. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[51]  R. Collier,et al.  Structure and activity of diphtheria toxin. II. Attack by trypsin at a specific site within the intact toxin molecule. , 1971, The Journal of biological chemistry.

[52]  D. Gill,et al.  Structure-activity relationships in diphtheria toxin. , 1971, The Journal of biological chemistry.

[53]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[54]  Y. Nishizuka,et al.  Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. , 1968, The Journal of biological chemistry.

[55]  R. Collier,et al.  Effect of diphtheria toxin on protein synthesis: inactivation of one of the transfer factors. , 1967, Journal of molecular biology.