Figure 3.

Eph receptor and ephrin signaling. (A) Interactions between EphB receptor and ephrinB ligand can trigger two mechanisms that underlie cell segregation. The first is mediated by interactions of EphB receptor with the metalloproteinase ADAM10 and with E-cadherin. On binding of EphB receptor to ephrinB ligand, ADAM10 activity cleaves E-cadherin, thus leading to decreased adhesion selectively at the Eph-ephrin interface. The second mechanism involves signaling pathways downstream from activated EphB receptor that lead to depolymerization of the actin cytoskeleton, with concommitant endocytosis of Eph-ephrin complexes. The combination of cytoskeletal collapse and cell disengagement leads to repulsion of EphB- by ephrinB-expressing cells. (B) Decreased E-cadherin-mediated adhesion between EphB and ephrinB cells establishes differential adhesion. Directional repulsion of EphB-expressing cells by ephrinB-expressing cells prevents intermingling. These two mechanisms may act together to establish and maintain cell segregation.