Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery.
Shigella use a special mechanism to invade epithelial cells called 'the trigger mechanism of entry', which allows epithelial cells to trap several bacteria simultaneously. On contact, Shigella deliver effectors into epithelial cells through the type III secretion system. Here, we show that one of the effectors, IpgB1, has a pivotal role in producing membrane ruffles by exploiting the RhoG-ELMO-Dock180 pathway to stimulate Rac1 activity. Using pulldown assays, we identified engulfment and cell motility (ELMO) protein as the IpgB1 binding partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by Shigella. Shigella invasiveness and IpgB1-induced ruffles were less in ELMO- and Dock180-knockdown cells compared with wild-type cells. Membrane association of ELMO-Dock180 with ruffles were promoted when cells expressed an IpgB1-ELMO chimera, establishing that IpgB1 mimics the role of RhoG in producing membrane ruffles. Taken together, our findings show that IpgB1 mimicry is the key to invasion by Shigella.
Handa
Yutaka
Y
Department of Microbiology and Immunology, Institute of Medical Science and University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Suzuki
Masato
M
Ohya
Kenji
K
Iwai
Hiroki
H
Ishijima
Nozomi
N
Koleske
Anthony J
AJ
Fukui
Yoshinori
Y
Sasakawa
Chihiro
C
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D021381:Protein Transport; D034622:RNA Interference; D012760:Shigella / Q000472:pathogenicity* / Q000502:physiology; D015398:Signal Transduction; D014161:Transduction, Genetic; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C099818:DOCK1 protein, human; C465214:ELMO1 protein, human; C508203:IpgB1 protein, Shigella flexneri; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein