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Toxins 2016, 8(5), 152; doi:10.3390/toxins8050152

New Insights into VacA Intoxication Mediated through Its Cell Surface Receptors

1
Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan
2
Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan
3
Cardiovascular and Pulmonary Branch, NHLBI, NIH, Building 10, Room 6D03, MSC 1590, Bethesda, MD 20892-1590, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Timothy L. Cover
Received: 4 February 2016 / Revised: 5 May 2016 / Accepted: 6 May 2016 / Published: 13 May 2016
(This article belongs to the Special Issue Vacuolating Toxin)
View Full-Text   |   Download PDF [667 KB, uploaded 13 May 2016]   |  

Abstract

Helicobacter pylori (H. pylori), a major cause of gastroduodenal diseases, produces VacA, a vacuolating cytotoxin associated with gastric inflammation and ulceration. The C-terminal domain of VacA plays a crucial role in receptor recognition on target cells. We have previously identified three proteins (i.e., RPTPα, RPTPβ, and LRP1) that serve as VacA receptors. These receptors contribute to the internalization of VacA into epithelial cells, activate signal transduction pathways, and contribute to cell death and gastric ulceration. In addition, other factors (e.g., CD18, sphingomyelin) have also been identified as cell-surface, VacA-binding proteins. Since we believe that, following interactions with its host cell receptors, VacA participates in events leading to disease, a better understanding of the cellular function of VacA receptors may provide valuable information regarding the mechanisms underlying the pleiotropic actions of VacA and the pathogenesis of H. pylori-mediated disease. In this review, we focus on VacA receptors and their role in events leading to cell damage. View Full-Text
Keywords: vacuolating cytotoxin (VacA); receptors; receptor-like protein tyrosine phosphatase (RPTP) α; RPTPβ; low-density lipoprotein receptor-related protein-1 (LRP1) vacuolating cytotoxin (VacA); receptors; receptor-like protein tyrosine phosphatase (RPTP) α; RPTPβ; low-density lipoprotein receptor-related protein-1 (LRP1)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Yahiro, K.; Hirayama, T.; Moss, J.; Noda, M. New Insights into VacA Intoxication Mediated through Its Cell Surface Receptors. Toxins 2016, 8, 152.

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