Interactions between Eph receptors and their membrane-bound ephrin ligands trigger bidirectional signalling cascades that regulate cell behaviour through effects on the cytoskeleton. Catherine Nobes and colleagues (p. ) now investigate how ephrin B family proteins – which regulate angiogenesis in normal and pathological contexts – modulate cell morphology and migration in vitro. Using microinjection techniques, the authors show that overexpression of ephrin-B2 increases membrane ruffling, and induces rapid cycles of cell contraction and expansion specifically in endothelial cell types. Compared with control cells, ephrin-B2-overexpressing cells also migrate faster and more randomly, similar to cancer cells. When isolated cells within a monolayer are microinjected with ephrin-B2, neighbouring cells repulse them, creating more space for movement of ephrin-B2-expressing cells. Notably, these effects require the cytoplasmic PDZ-binding motif of ephrin-B2, suggesting that association with other intracellular signalling molecules is important for ephrin-B2 function. Finally, the authors show that these effects are independent of the ephrin-B2 receptor, EphB4, when ephrin-B2 is overexpressed, suggesting that ephrin-B2 can act cell autonomously. Therefore, the authors conclude, ephrin-B2 activation triggers multiple downstream events that can be EphB4-dependent and -independent.
