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@ARTICLE{Kemmerling:829414,
author = {Kemmerling, Nadja and Wunderlich, Patrick and Theil, Sandra
and Linnartz-Gerlach, Bettina and Hersch, Nils and Hoffmann,
Bernd and Heneka, Michael T. and de Strooper, Bart and
Neumann, Harald and Walter, Jochen},
title = {{I}ntramembranous processing by γ-secretase regulates
reverse signaling of ephrin-{B}2 in migration of microglia},
journal = {Glia},
volume = {65},
number = {7},
issn = {0894-1491},
address = {Bognor Regis [u.a.]},
publisher = {Wiley-Liss},
reportid = {FZJ-2017-03118},
pages = {1103–1118},
year = {2017},
abstract = {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.},
cin = {ICS-7},
ddc = {610},
cid = {I:(DE-Juel1)ICS-7-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000401345400007},
pubmed = {pmid:28370426},
doi = {10.1002/glia.23147},
url = {https://juser.fz-juelich.de/record/829414},
}