Cholesterol-rich Membrane Microdomains Mediate Cell Cycle Arrest Induced by Actinobacillus Actinomycetemcomitans Cytolethal-distending Toxin

Overview

Journal Cell Microbiol

Publisher Wiley

Specialties Cell Biology
Microbiology

Date 2006 Apr 14

PMID 16611231

Citations 44

Authors

Kathleen Boesze-Battaglia

Dave Besack

Terry McKay

Ali Zekavat

Linda Otis

Kelly Jordan-Sciutto

Bruce J Shenker

Affiliations

Soon will be listed here.

Abstract

We have previously shown that Actinobacillus actinomycetemcomitans cytolethal-distending toxin (Cdt) is a potent immunosuppressive agent that induces G2/M arrest in human lymphocytes. In this study, we explored the possibility that Cdt-mediated immunotoxicity involves lipid membrane microdomains. We first determined that following treatment of Jurkat cells with Cdt holotoxin all three Cdt subunits localize to these microdomains. Laser confocal microscopy was employed to colocalize the subunits with GM1-enriched membrane regions which are characteristic of membrane rafts. Western blot analysis of isolated lipid rafts also demonstrated the presence of Cdt peptides. Cholesterol depletion, using methyl beta-cyclodextrin, protected cells from the ability of the Cdt holotoxin to induce G2 arrest. Moreover, cholesterol depletion reduced the ability of the toxin to associate with Jurkat cells. Thus, lipid raft integrity is vital to the action of Cdt on host cells. The implications of our observations with respect to Cdt mode of action are discussed.

Citing Articles

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Boesze-Battaglia K, Cohen G, Bates P, Walker L, Zekavat A, Shenker B Front Cell Infect Microbiol. 2024; 14:1334224.

PMID: 38698905 PMC: 11063343. DOI: 10.3389/fcimb.2024.1334224.

Cytolethal Distending Toxin Induces Cellugyrin-(Synaptogyrin 2) Dependent Cellular Senescence in Oral Keratinocytes.

Shenker B, Korostoff J, Walker L, Zekavat A, Dhingra A, Kim T Pathogens. 2024; 13(2).

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Revisiting bacterial cytolethal distending toxin structure and function.

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Cytolethal Distending Toxin-Induces Cell Cycle Arrest in a Glycogen Synthase Kinase (GSK)-3-Dependent Manner in Oral Keratinocytes.

Shenker B, Walker L, Zekavat A, Korostoff J, Boesze-Battaglia K Int J Mol Sci. 2022; 23(19).

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