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000829414 1001_ $$0P:(DE-HGF)0$$aKemmerling, Nadja$$b0
000829414 245__ $$aIntramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia
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000829414 520__ $$aThe Eph-ephrin system plays pivotal roles in cell adhesion and migration. The receptor-like functions of the ephrin ligands allow the regulation of intracellular processes via reverse signaling. γ-Secretase mediated processing of ephrin-B has previously been linked to activation of Src, a kinase crucial for focal adhesion and podosome phosphorylation. Here, we analyzed the role of γ-secretase in the stimulation of reverse ephrin-B2 signaling in the migration of mouse embryonic stem cell derived microglia. The proteolytic generation of the ephrin-B2 intracellular domain (ICD) by γ-secretase stimulates Src and focal adhesion kinase (FAK). Inhibition of γ-secretase decreased the phosphorylation of Src and FAK, and reduced cell motility. These effects were associated with enlargement of the podosomal surface. Interestingly, expression of ephrin-B2 ICD could rescue these effects, indicating that this proteolytic fragment mediates the activation of Src and FAK, and thereby regulates podosomal dynamics in microglial cells. Together, these results identify γ-secretase as well as ephrin-B2 as regulators of microglial migration.
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000829414 7001_ $$0P:(DE-HGF)0$$aWunderlich, Patrick$$b1
000829414 7001_ $$0P:(DE-HGF)0$$aTheil, Sandra$$b2
000829414 7001_ $$0P:(DE-HGF)0$$aLinnartz-Gerlach, Bettina$$b3
000829414 7001_ $$0P:(DE-Juel1)128815$$aHersch, Nils$$b4$$ufzj
000829414 7001_ $$0P:(DE-Juel1)128817$$aHoffmann, Bernd$$b5$$ufzj
000829414 7001_ $$0P:(DE-HGF)0$$aHeneka, Michael T.$$b6
000829414 7001_ $$0P:(DE-HGF)0$$ade Strooper, Bart$$b7
000829414 7001_ $$0P:(DE-HGF)0$$aNeumann, Harald$$b8
000829414 7001_ $$0P:(DE-HGF)0$$aWalter, Jochen$$b9$$eCorresponding author
000829414 773__ $$0PERI:(DE-600)1474828-9$$a10.1002/glia.23147$$n7$$p1103–1118$$tGlia$$v65$$x0894-1491$$y2017
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