TY - JOUR
T1 - A chemoattractant-mediated Gi-coupled pathway activates adenylyl cyclase in human neutrophils
AU - Mahadeo, Dana C.
AU - Janka-Junttila, Mirkka
AU - Smoot, Rory L.
AU - Roselova, Pavla
AU - Parent, Carole A.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E06-05-0418
DO - 10.1091/mbc.E06-05-0418
M3 - Article
C2 - 17135293
AN - SCOPUS:33846849167
SN - 1059-1524
VL - 18
SP - 512
EP - 522
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 2
ER -