Saltar al contenido
Merck

Intramembranous processing by γ-secretase regulates reverse signaling of ephrin-B2 in migration of microglia.

Glia (2017-04-04)
Nadja Kemmerling, Patrick Wunderlich, Sandra Theil, Bettina Linnartz-Gerlach, Nils Hersch, Bernd Hoffmann, Michael T Heneka, Bart de Strooper, Harald Neumann, Jochen Walter
RESUMEN

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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Anti-β-actina, anticuerpo monoclonal, clone AC-15, purified from hybridoma cell culture
Sigma-Aldrich
Anticuerpo anti-fosfotirosina, clon 4G10 ®, clone 4G10®, Upstate®, from mouse
Sigma-Aldrich
Anti-Ephrin-B2 Antibody, clone 10H1.1, from mouse
Sigma-Aldrich
Anti-EFNB2 (Ab-316) antibody produced in rabbit, affinity isolated antibody