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Expression of mutant dynamin protects cells against diphtheria toxin but not against ricin.
Exp Cell Res. 1998 Mar 15; 239(2):293-300.EC

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 non-transfected 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.

Authors+Show Affiliations

Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9521846

Citation

Simpson, J C., et al. "Expression of Mutant Dynamin Protects Cells Against Diphtheria Toxin but Not Against Ricin." Experimental Cell Research, vol. 239, no. 2, 1998, pp. 293-300.
Simpson JC, Smith DC, Roberts LM, et al. Expression of mutant dynamin protects cells against diphtheria toxin but not against ricin. Exp Cell Res. 1998;239(2):293-300.
Simpson, J. C., Smith, D. C., Roberts, L. M., & Lord, J. M. (1998). Expression of mutant dynamin protects cells against diphtheria toxin but not against ricin. Experimental Cell Research, 239(2), 293-300.
Simpson JC, et al. Expression of Mutant Dynamin Protects Cells Against Diphtheria Toxin but Not Against Ricin. Exp Cell Res. 1998 Mar 15;239(2):293-300. PubMed PMID: 9521846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of mutant dynamin protects cells against diphtheria toxin but not against ricin. AU - Simpson,J C, AU - Smith,D C, AU - Roberts,L M, AU - Lord,J M, PY - 1998/4/2/pubmed PY - 1998/4/2/medline PY - 1998/4/2/entrez SP - 293 EP - 300 JF - Experimental cell research JO - Exp. Cell Res. VL - 239 IS - 2 N2 - 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 non-transfected 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. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/9521846/Expression_of_mutant_dynamin_protects_cells_against_diphtheria_toxin_but_not_against_ricin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(97)93921-5 DB - PRIME DP - Unbound Medicine ER -