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.
Highlights
Helicobacter pylori (H. pylori) is a helical-shaped gram-negative microorganism, which colonizes the human stomach and plays important roles in the pathogenesis of gut diseases (e.g., gastric inflammation, ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, gastric cancer [1]), and chronic idiopathic thrombocytopenic purpura [2]
We show that VacA receptors are associated with the regulation of cellular events including autophagy and apoptosis
Through immunoprecipitation with an anti-VacA antibody, receptor-like protein tyrosine phosphatase (RPTP) β was identified as a VacA receptor [29]
Summary
Helicobacter pylori (H. pylori) is a helical-shaped gram-negative microorganism, which colonizes the human stomach and plays important roles in the pathogenesis of gut diseases (e.g., gastric inflammation, ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, gastric cancer [1]), and chronic idiopathic thrombocytopenic purpura [2]. 55 kDa (p55) plays an important role in binding to toxin receptors on cell membranes [6,7,8,9,10]. Identical in amino acid sequence [11] These two types of VacA have different affinities for cell-surface receptors [8,12,13] and show different cell specificities [14]. Analysis of p55 crystal structure and amino acids sequence showed that conserved regions for oligomerization are in the N-terminal domain, and in the C-terminal domain including two β-helical structures and a disulfide-linked domain. Toxins 2016, 8, 152 associated with a higher risk of gastric ulcer than are m2 strains [15] These different sequences may reflect receptor-binding affinities of m1 and m2 VacA. We show that VacA receptors are associated with the regulation of cellular events including autophagy and apoptosis
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