tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing vav2-rhoa-mediated cytoskeletal rearrangements酪氨酸磷酸化caveolin-1块细菌吸收诱导vav2-rhoa-mediated细胞骨架重组.pdfVIP

Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements 1. 1¤a. 1¤b. 2 Jan Peter Boettcher , Marieluise Kirchner , Yuri Churin , Alexis Kaushansky , Malvika 1 1¤c 1 2 1 Pompaiah , Hans Thorn , Volker Brinkmann , Gavin MacBeath , Thomas F. Meyer * 1 Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany, 2 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America Abstract Certain bacterial adhesins appear to promote a pathogen’s extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P+GC) induces an immediate recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake.