Phosphoinositide 3-kinase γ ties chemoattractant- and adrenergic control of microglial motility.
Microglial motility is tightly controlled by multitude of agonistic and antagonistic factors. Chemoattractants, released after infection or damage of the brain, provoke directed migration of microglia to the pathogenic incident. In contrast, noradrenaline and other stress hormones have been shown to suppress microglial movement. Here we asked for the signaling reactions involved in the positive and negative control of microglial motility. Using pharmacological and genetic approaches we identified the lipid kinase activity of phosphoinositide 3-kinase species γ (PI3Kγ) as an essential mediator of microglial migration provoked by the complement component C5a and other chemoattractants. Inhibition of PI3Kγ lipid kinase activity by protein kinase A was disclosed as mechanism causing suppression of microglial migration by noradrenaline. Together these data characterize PI3Kγ as a nodal point in the control of microglial motility.
Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), University Hospital of Jena, Hans -Knöll -Straße 2, 07745 Jena, Germany. Electronic address: Nadine.Schneble@med.uni-jena.de.
Nadine
N
Schneble
Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), University Hospital of Jena, Hans -Knöll -Straße 2, 07745 Jena, Germany. Electronic address: Caroline.Schmidt@med.uni-jena.de.
Caroline
C
Schmidt
Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), University Hospital of Jena, Hans -Knöll -Straße 2, 07745 Jena, Germany. Electronic address: Reinhard.Bauer@med.uni-jena.de.
Reinhard
R
Bauer
Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), University Hospital of Jena, Hans -Knöll -Straße 2, 07745 Jena, Germany. Electronic address: Joerg.Mueller2@med.uni-jena.de.
Jörg P
JP
Müller
Leibnitz Institute for Age Research, Fritz Lipmann Institute (FLI), Beutenberg-Straße 11, 07745 Jena, Germany. Electronic address: shamci@fli-leibniz.de.
Shamci
S
Monajembashi
Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), University Hospital of Jena, Hans -Knöll -Straße 2, 07745 Jena, Germany. Electronic address: Reinhard.Wetzker@uni-jena.de.
Reinhard
R
Wetzker
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis; D015936:Complement C5a / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D002630:Chemotactic Factors; D015936:Complement C5a; D019869:Phosphatidylinositol 3-Kinases; D009638:Norepinephrine
CNS; Chemotaxis; Immune system; Microglia; PI3Kγ