Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements

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. further,our data establish a mechanistic link between cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function. © 2010 boettcher et al.