ephrins

Ephrins are a family of membrane-bound ligands for the Eph receptor tyrosine kinases. They are subdivided into ephrin-A ligands, which are anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor, and ephrin-B ligands, which are transmembrane proteins with a cytoplasmic tail. Ephrins are not secreted; signaling requires cell–cell contact between a cell expressing an Eph receptor and a neighboring cell expressing an ephrin ligand.

Eph receptors (EphA and EphB subclasses) are receptor tyrosine kinases. Binding of an ephrin to its Eph receptor triggers forward signaling in the receptor-expressing cell, often affecting cytoskeletal dynamics and adhesion. Because ephrins are membrane-bound, signaling can also occur in the ligand-expressing cell, a process known as reverse signaling. The interaction is usually high-affinity and can be bidirectional, with different downstream effectors in the two cells.

Biological outcomes include regulation of cell positioning, boundary formation between tissues, axon guidance, and synaptic organization. In the nervous system, ephrin–Eph signaling guides axons and contributes to retinotopic mapping and topographic organization. In the vasculature, Eph/ephrin signaling influences angiogenesis and vessel remodeling. The pathways commonly involve modulation of Rho family GTPases, phosphorylation cascades, and interactions with PDZ-domain proteins.

Ephrins play roles in development and disease. Altered Eph/ephrin signaling is implicated in cancer progression, metastasis, and tumor angiogenesis. Because of their cell–cell contact requirement and role in cell positioning, they are of interest in developmental biology as well as therapeutic research.