%0 Journal Article
%A Kemmerling, Nadja
%A Wunderlich, Patrick
%A Theil, Sandra
%A Linnartz-Gerlach, Bettina
%A Hersch, Nils
%A Hoffmann, Bernd
%A Heneka, Michael T.
%A de Strooper, Bart
%A Neumann, Harald
%A Walter, Jochen
%T Intramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia
%J Glia
%V 65
%N 7
%@ 0894-1491
%C Bognor Regis [u.a.]
%I Wiley-Liss
%M FZJ-2017-03118
%P 1103–1118
%D 2017
%X The 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000401345400007
%$ pmid:28370426
%R 10.1002/glia.23147
%U https://juser.fz-juelich.de/record/829414