The Journal of Neuroscience, February 15, 2003, 23(4):1198
Involvement of the Neurotensin Receptor-3 in the
Neurotensin-Induced Migration of Human Microglia
Stéphane
Martin,
Jean-Pierre
Vincent, and
Jean
Mazella
Institut de Pharmacologie Moléculaire et Cellulaire,
Unité Mixte de Recherche 6097 du Centre National de la Recherche
Scientifique, Sophia Antipolis, 06560 Valbonne, France
Microglia motility plays a crucial role in response to lesion or
exocytotoxic damage of the cerebral tissue. We used two in vitro assays, a wound-healing model and a chemotaxis assay, to show that the neuropeptide neurotensin elicited the migration of the
human microglial cell line C13NJ by a mechanism dependent on both
phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways. The effect of neurotensin on cell migration was blocked by the neurotensin receptor-3 propeptide, a
selective ligand of this receptor. We demonstrate, by using RT-PCR,
photoaffinity labeling, and Western blot analysis, that the type I
neurotensin receptor-3 was the only known neurotensin receptor
expressed in these microglial cells and that its activation led to the
phosphorylation of both extracellular signal-regulating kinases 1/2 and
Akt. Furthermore, the effect of neurotensin on cell migration was
preceded by a profound modification of the F-actin cytoskeleton,
particularly by the rapid formation of numerous cell filopodia. Both
the motility and the filopodia appearance induced by neurotensin were
totally blocked by selective inhibitors of MAP kinases or PI 3-kinase
pathways. This demonstrates that the neurotensin receptor-3 is
functional and mediates the migratory actions of neurotensin.
Key words:
human microglia; neurotensin receptor-3; signaling; sortilin; migration; PI 3-kinase; MAP kinase
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341198-08$05.00/0
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