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PNAS 98 (16): 9086-9091

Copyright © 2001 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

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

Nancy McNamara*, Amy Khong*, David McKemy{dagger}, Mike Caterina{dagger}, Jose Boyer{ddagger}, David Julius{dagger}, and Carol Basbaum*,§

Departments of *Anatomy and {dagger}Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0452; and {ddagger}Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599-7365

Accepted for publication June 11, 2001.

Received for publication February 6, 2001.

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.


§ To whom reprint requests should be addressed. E-mail: cbas{at}itsa.ucsf.edu.

Communicated by John A. Clements, University of California, San Francisco, CA

Bryan, R., Ratner, A., Heyer, G., Nguyen, B., Davis, M. B., Heath, M., Cheung, A. A., Weiser, J. & Prince, A. Ninety-ninth General Meeting of the American Society of Microbiology, June 1, 1999, Chicago, IL, abstr. B/D-245, p. 77.

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