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Membrane translocation of diphtheria toxin fragment A exploits early to late endosome trafficking machinery
Author(s) -
Lemichez Emmanuel,
Bomsel Morgane,
Devilliers Ginette,
Spek Johanna,
Murphy John R.,
Lukianov Evgenij V.,
Olsnes Sjur,
Boquet Patrice
Publication year - 1997
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1997.tb02669.x
Subject(s) - endosome , endocytic cycle , endocytosis , biology , cytosol , microbiology and biotechnology , diphtheria toxin , biochemistry , toxin , cell , intracellular , enzyme
Summary 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.