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.
Boettcher
Jan Peter
JP
Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
Kirchner
Marieluise
M
Churin
Yuri
Y
Kaushansky
Alexis
A
Pompaiah
Malvika
M
Thorn
Hans
H
Brinkmann
Volker
V
Macbeath
Gavin
G
Meyer
Thomas F
TF
D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology*; D010861:Fimbriae, Bacterial / Q000378:metabolism; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity* / Q000502:physiology; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D051242:Caveolin 1; D051567:Proto-Oncogene Proteins c-vav; C093651:VAV2 protein, human; C066737:RHOA protein, human; D014443:Tyrosine; D020742:rhoA GTP-Binding Protein
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