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Infection and Immunity, June 2008, p. 2296-2303, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01573-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Involvement of Vesicle-Associated Membrane Protein 7 in Human Gastric Epithelial Cell Vacuolation Induced by Helicobacter pylori-Produced VacA{triangledown}

Hirosato Mashima,1* Junko Suzuki,1 Toshiya Hirayama,2 Yukako Yoshikumi,1 Hideki Ohno,1 Hirohide Ohnishi,3 Hiroshi Yasuda,4 Toshiro Fujita,5 and Masao Omata1

Departments of Gastroenterology,1 Endocrinology and Nephrology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan,5 Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan,2 Division of Gastroenterology and Neurology, Akita University School of Medicine, Akita 010-8543, Japan,3 Division of Gastroenterology, Showa University Fujigaoka Hospital, Kanagawa 227-8501, Japan4

Received 29 November 2007/ Returned for modification 11 January 2008/ Accepted 12 March 2008

Helicobacter pylori-produced cytotoxin VacA induces intracellular vacuolation. The VacA-induced vacuole is assumed to represent the pathological status of intracellular trafficking. The fusion mechanism of the endosomes requires the formation of a tight complex between the Q-SNAREs and the R-SNAREs. We recently reported that syntaxin 7, a family member of the Q-SNARE protein, is involved in VacA-induced vacuole formation. In order to further elucidate the molecular mechanism, we identified the participation of vesicle-associated membrane protein 7 (VAMP7) as a partner of syntaxin 7. Immunocytochemistry revealed endogenous VAMP7 to be localized to the vacuoles induced by VacA. A Northern blotting study demonstrated that VacA intoxication increased VAMP7 mRNA in a time-dependent manner. VAMP7 was coimmunoprecipitated with syntaxin 7, and the amounts of endogenous VAMP7 and syntaxin 7 bound to syntaxin 7 and VAMP7, respectively, increased in response to VacA. The down-regulation of VAMP7 using small interfering RNA inhibited VacA-induced vacuolation, and the transient transfection of dominant-negative mutant VAMP7, the N-terminal domain of VAMP7, also inhibited the vacuolation. We therefore conclude that R-SNARE VAMP7 plays an important role in VacA-induced vacuolation as a partner of Q-SNARE syntaxin 7.

* Corresponding author. Mailing address: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Phone: 81-3-3815-5411, ext. 37194. Fax: 81-3-5800-9738. E-mail: hmashima1-tky{at}umin.ac.jp

{triangledown} Published ahead of print on 24 March 2008.

Editor: S. R. Blanke

Infection and Immunity, June 2008, p. 2296-2303, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01573-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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