TY  - JOUR
AU  - Kemmerling, Nadja
AU  - Wunderlich, Patrick
AU  - Theil, Sandra
AU  - Linnartz-Gerlach, Bettina
AU  - Hersch, Nils
AU  - Hoffmann, Bernd
AU  - Heneka, Michael T.
AU  - de Strooper, Bart
AU  - Neumann, Harald
AU  - Walter, Jochen
TI  - Intramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia
JO  - Glia
VL  - 65
IS  - 7
SN  - 0894-1491
CY  - Bognor Regis [u.a.]
PB  - Wiley-Liss
M1  - FZJ-2017-03118
SP  - 1103–1118
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000401345400007
C6  - pmid:28370426
DO  - DOI:10.1002/glia.23147
UR  - https://juser.fz-juelich.de/record/829414
ER  -