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

Nancy McNamara, Amy Khong, David McKemy, Mike Caterina, Jose Boyer, David Julius, Carol Basbaum

Research output: Contribution to journalArticlepeer-review

Abstract

The flagella of the Gram-negative bacterium Pseudomonas aeruginosa serve not only for motility but also to bind bacteria to the host cell glycolipid asialoGM1 (ASGM1) through the protein flagellin. This interaction triggers defensive responses in host cells. How this response occurs is unclear because ASGM1 lacks transmembrane and cytoplasmic domains and there is little information about the downstream effectors that connect ASGM1 ligation to the initiation of host defense responses. Here, we show that ASGM1 ligation promotes ATP release from the host cell, followed by autocrine activation of a nucleotide receptor. This response links ASGM1 to cytoplasmic signaling molecules and results in activation of phospholipase C, Ca2+ mobilization, phosphorylation of a mitogen-activated protein kinase (Erk 1/2), and activation of mucin transcription. These results indicate that bacterial interaction with host cells can trigger autocrine nucleotide signaling and suggest that agents affecting nucleotide receptors may modulate host responses to bacteria.

Original languageEnglish (US)
Pages (from-to)9086-9091
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number16
DOIs
StatePublished - Jul 31 2001
Externally publishedYes

ASJC Scopus subject areas

  • General

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