大野 秀樹
   Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA
Journal Formal name:J Biol Chem
ISSN code:0021-9258 (Print) 0021-9258 (Linking)
Domestic / ForeginForegin
Volume, Issue, Page 278,pp.25585-25590
Author and coauthor Suzuki, J Ohnishi, H Wada, A Hirayama, T Ohno, H Ueda, N Yasuda, H Iiri, T Wada, Y Futai, M Mashima, H
Publication date 2003
Summary The Helicobacter pylori-produced cytotoxin VacA induces intracellular vacuolation. The formed vacuole is assumed to be a hybrid of late endosome and lysosome. To elucidate the molecular mechanism of VacA-induced vacuolation, we examined the participation of syntaxin 7 in the human gastric epithelial cell line AGS. Immunocytochemistry revealed that endogenous syntaxin 7 was localized to vacuoles induced by VacA. Northern and Western blotting demonstrated that VacA intoxication increased syntaxin 7 mRNA and protein expression, respectively, in a time-dependent manner. Transient transfection of dominant-negative mutant syntaxin 7, which lacks a carboxyl-terminal transmembrane domain, inhibited VacA-induced vacuolation. In contrast, transient transfection of wild-type syntaxin 7, dominant-negative mutant syntaxin 1a, or dominant-negative mutant syntaxin 4 did not alter VacA-induced vacuolation. Furthermore, under VacA treatment, neutral red dye uptake, a parameter of VacA-induced vacuolation, was inhibited in cells stably transfected with mutant syntaxin 7 but not in cells stably transfected with wild-type syntaxin 7, mutant syntaxin 1a, or mutant syntaxin 4. Sequential immunocytochemical observation confirmed that expression of mutant syntaxin 7 did not affect VacA attachment to or internalization into AGS cells. We suggest that syntaxin 7 is involved in the intracellular vacuolation induced by VacA.
DOI 10.1074/jbc.M212445200
Document No. 12730232