MEMBRANE TRANSLOCATION OF DIPHTHERIA-TOXIN FRAGMENT - A EXPLOITS EARLY TO LATE ENDOSOME TRAFFICKING MACHINERY

Citation
E. Lemichez et al., MEMBRANE TRANSLOCATION OF DIPHTHERIA-TOXIN FRAGMENT - A EXPLOITS EARLY TO LATE ENDOSOME TRAFFICKING MACHINERY, Molecular microbiology, 23(3), 1997, pp. 445-457
Citations number
59
Categorie Soggetti
Biology,Microbiology
Journal title
ISSN journal
0950382X
Volume
23
Issue
3
Year of publication
1997
Pages
445 - 457
Database
ISI
SICI code
0950-382X(1997)23:3<445:MTODF->2.0.ZU;2-Z
Abstract
After reaching early endosomes by receptor-mediated endocytosis, dipht heria toxin (DT) molecules have two possible fates. A large pool enter s the degradative pathway whereas a few molecules become cytotoxic by translocating their catalytic fragment A (DTA) into the cytosol. Impai rment of DT degradation by microtubule depolymerization does not block DT cytotoxicity. Therefore, DTA membrane translocation into the cytos ol occurs from an endocytic compartment located upstream of late endos omes. Comparisons between early endosomes and endocytic carrier vesicl es in a cell-free translocation assay have demonstrated that early end osomes are the earliest endocytic compartment from which DTA transloca tes. DTA translocation is ATP-dependent, requires early endosomal acid ification, and is increased by the addition of cytosol. Cytosol-depend ent DTA translocation is GTP gamma S-insensitive but is blocked by ant i-beta COP antibodies.