Editors' ChoiceCell Biology

The Glycolipid Defense

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Science's STKE  07 Aug 2001:
Vol. 2001, Issue 94, pp. tw11
DOI: 10.1126/stke.2001.94.tw11

Host cells can recognize the protein flagellin, which is a common component of bacterial flagella, and this contributes to host defense against infection. Asialoganglioside M1 (ASGM1) is a glycolipid present on the surface of epithelial cells that binds flagellin and initiates host-cell defense responses, such as cytokine and mucin production. McNamara et al. show that agents that bind ASGM1 (flagellin or an antibody against ASGM1) stimulate an increase in extracellular adenosine triphosphate (ATP), which activates purinergic PY2 receptors, leading to increased mucin expression. Increases in mucin expression were measured by a reporter gene assay, and treatment of the cells with specific inhibitors of PY2 receptors that blocked mucin expression confirmed PY2 receptor involvement. Increased mucin expression in response to ASGM1 binding also required activation of phospholipase C and an increase in intracellular [Ca2+], which is consistent with the activation of G protein-coupled PY2 receptors. ASGM1 binding led to increased phosphorylation of extracellular signal-regulated kinases 1 and 2, but increased mucin expression was only partially blocked by inhibition of the upstream kinases MEK1 and MEK2, suggesting that at least two pathways downstream of the calcium transient for increased mucin expression. Whereas the intracellular signaling pathways are becoming well delineated for host responses to flagellin exposure, the mechanism by which binding of an extracellular glycolipid can trigger ATP release remains unknown.

N. McNamara, A. Khong, D. McKemy, M. Caterina, J. Boyer, D. Julius, C. Basbaum, ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor. Proc. Natl. Acad. Sci. U.S.A. 98, 9086-9091 (2001). [Abstract] [Full Text]

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