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Expression of mutant dynamin protects cells against diphtheria toxin but not against ricin

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UNSPECIFIED (1998) Expression of mutant dynamin protects cells against diphtheria toxin but not against ricin. EXPERIMENTAL CELL RESEARCH, 239 (2). pp. 293-300. ISSN 0014-4827

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Abstract

Diphtheria toxin is believed to enter sensitive mammalian cells via receptor-mediated endocytosis from clathrin-coated pits, while ricin can enter via both clathrin-dependent and clathrin-independent endocytosis. The present study has confirmed this by determining the toxin sensitivity of COS-7y cells which were transiently overexpressing a trans dominant negative mutant of dynamin, a GTPase required for the budding of clathrin-coated vesicles from the plasma membrane. Cells overexpressing wild-type dynamin showed normal receptor-mediated endocytosis of transferrin and remained sensitive to both diphtheria toxin and ricin. Cells overexpressing a mutant dynamin defective in GTP binding and hydrolysis were unable to endocytose transferrin and were protected against diphtheria toxin, but they remained completely sensitive to ricin intoxication. Treating nontransfected cells or cells overexpressing mutant dynamin with nystatin caused a redistribution of the caveolae membrane marker protein VIP21-caveolin from the cell surface to intracellular locations, but did not affect their sensitivity to ricin. The redistribution of caveolin seen after nystatin treatment may reflect the disappearance of caveolae. If this is the case, caveolae are not responsible for the endocytosis of ricin. An alternative clathrin-independent route may operate for ricin, since cellular uptake, intracellular transport, and translocation into the cytosol remain unaffected when clathrin-dependent endocytosis is effectively blocked. (C) 1998 Academic Press.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QH Natural history > QH301 Biology
Journal or Publication Title: EXPERIMENTAL CELL RESEARCH
Publisher: ACADEMIC PRESS INC
ISSN: 0014-4827
Date: 15 March 1998
Volume: 239
Number: 2
Number of Pages: 8
Page Range: pp. 293-300
Publication Status: Published
URI: http://wrap.warwick.ac.uk/id/eprint/15892

Data sourced from Thomson Reuters' Web of Knowledge

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