De novo formation of focal complex-like structures in host cells by invading Streptococci.
Group A streptococcus (GAS) induces its own entry into eukaryotic cells in vitro and in vivo. Fibronectin (Fn) bound to protein F1, a GAS surface protein, acts as a bridge connecting the bacterium to host cell integrins. This triggers clustering of integrins, which acquire a polar pattern of distribution similar to that of protein F1 on the GAS surface. A unique and transient adhesion complex is formed at the site of GAS entry, which does not contain alpha-actinin. Vinculin is recruited to the site of GAS entry but is not required for uptake. The invading GAS recruits focal adhesion kinase (FAK), which is required for uptake and is tyrosine phosphorylated. The Src kinases, Src, Yes and Fyn, enhance the efficiency of GAS uptake but are not absolutely required for GAS entry. In addition, Rac and Cdc42, but not Rho, are required for the entry process. We suggest a model in which integrin engagement by Fn-occupied protein F1 triggers two independent signalling pathways. One is initiated by FAK recruitment and tyrosine phosphorylation, whereas the other is initiated by the recruitment and activation of Rac. The two pathways subsequently converge to trigger actin rearrangement leading to bacterial uptake.
Ozeri
V
V
Department of Clinical Microbiology, The Hebrew University-Hadassah Medical School, Jerusalem 91010, Israel.
Rosenshine
I
I
Ben-Ze'Ev
A
A
Bokoch
G M
GM
Jou
T S
TS
Hanski
E
E
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D004705:Endocytosis; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction; D013291:Streptococcus / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D018829:Adhesins, Bacterial; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; C078635:fibronectin-binding proteins, bacterial; D000185:Actinin; D016596:Vinculin; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D020559:Monomeric GTP-Binding Proteins