| First Author | Kemmerling N | Year | 2017 |
| Journal | Glia | Volume | 65 |
| Issue | 7 | Pages | 1103-1118 |
| PubMed ID | 28370426 | Mgi Jnum | J:242838 |
| Mgi Id | MGI:5906943 | Doi | 10.1002/glia.23147 |
| Citation | Kemmerling N, et al. (2017) Intramembranous processing by gamma-secretase regulates reverse signaling of ephrin-B2 in migration of microglia. Glia 65(7):1103-1118 |
| abstractText | 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. gamma-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 gamma-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 gamma-secretase stimulates Src and focal adhesion kinase (FAK). Inhibition of gamma-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 gamma-secretase as well as ephrin-B2 as regulators of microglial migration. |
