Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion

Eph receptor tyrosine kinases and their corresponding surface-bound ligands , the ephrins, provide cues to the migration of cells and growth cones duri ng embryonic development. Here we show that ephrin-A5, which is attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidylinosito l-anchor, induces compartmentalized signaling within a caveolae-like membra ne microdomain when bound to the extracellular domain of its cognate Eph re ceptor. The physiological response induced by this signaling event is conco mitant with a change in the cellular architecture and adhesion of the ephri n-A5-expressing cells and requires the activity of the Fyn protein tyrosine kinase. This study stresses the relevance of bidirectional signaling invol ving the ephrins and Eph receptors during brain development.