PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis.
Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P(3), but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A(2). Loss of this gene did not alter PI(3,4,5)P(3) regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA(2) activity. Deletion of the PLA(2) homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA(2) homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA(2) and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA(2) may be important mediators of the response.
Chen
Lingfeng
L
Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Iijima
Miho
M
Tang
Ming
M
Landree
Mark A
MA
Huang
Yi Elaine
YE
Xiong
Yuan
Y
Iglesias
Pablo A
PA
Devreotes
Peter N
PN
D000199:Actins / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002449:Cell Aggregation; D002478:Cells, Cultured; D002633:Chemotaxis; D000242:Cyclic AMP / Q000494:pharmacology; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism; D054467:Phospholipases A2; D015398:Signal Transduction
D000199:Actins; D016718:Arachidonic Acid; D000242:Cyclic AMP; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; C118303:phosphoinositide-3,4,5-triphosphate