A chemoattractant-mediated Gi-coupled pathway activates adenylyl cyclase in human neutrophils

Dana C. Mahadeo, Mirkka Janka-Junttila, Rory L. Smoot, Pavla Roselova, Carole A. Parent

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Neutrophils and Dictyostelium use conserved signal transduction pathways to decipher chemoattractant gradients and migrate directionally. In both cell types, addition of chemoattractants stimulates the production of cAMP, which has been suggested to regulate chemotaxis. We set out to define the mechanism by which chemoattractants increase cAMP levels in human neutrophils. We show that chemoattractants elicit a rapid and transient activation of adenylyl cyclase (AC). This activation is sensitive to pertussis toxin treatment but independent of phosphoinositide-3 kinase activity and an intact cytoskeleton. Remarkably, and in sharp contrast to Gαs-mediated activation, chemoattractant-induced AC activation is lost in cell lysates. Of the nine, differentially regulated transmembrane AC isoforms in the human genome, we find that isoforms III, IV, VII, and IX are expressed in human neutrophils. We conclude that the signal transduction cascade used by chemoattractants to activate AC is conserved in Dictyostelium and human neutrophils and is markedly different from the canonical Gαs-meditated pathway.

Original languageEnglish (US)
Pages (from-to)512-522
Number of pages11
JournalMolecular biology of the cell
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Mahadeo, D. C., Janka-Junttila, M., Smoot, R. L., Roselova, P., & Parent, C. A. (2007). A chemoattractant-mediated Gi-coupled pathway activates adenylyl cyclase in human neutrophils. Molecular biology of the cell, 18(2), 512-522. https://doi.org/10.1091/mbc.E06-05-0418