ATP transducer signals from ASGM1, a glycolipid that functions as a bacterial receptor

The flagella of the Gram-negative bacterium Pseudomonas aeruginosa serve no t only for motility but also to bind bacteria to the host calf glycolipid a sialoGM1 (ASGM1} through the protein flagellin. This interaction triggers d efensive responses in host cells. How this response occurs is unclear becau se ASGM1 lacks transmembrane and cytoplasmic domains and there is little in formation about the downstream effectors that connect ASGM1 ligation to the initiation of host defense responses. Here, we show that ASGM1 ligation pr omotes ATP release from the host cell, followed by autocrine activation of a nucleotide receptor. This response links ASGM1 to cytoplasmic signaling m olecules and results in activation of phospholipase C, Ca2+ mobilization, p hosphorylation of a mitogen-activated protein kinase (Erk 1/2}; and activat ion of mucin transcription. These results indicate that bacterial interacti on with host cells can trigger autocrine nucleotide signaling and suggest t hat agents affecting nucleotide receptors may modulate host responses to ba cteria.