EphrinB

Ephrin-B refers to a family of membrane-anchored ligands for Eph receptor tyrosine kinases, encoded in humans by EFNB1, EFNB2, and EFNB3. These transmembrane ligands engage Eph receptors on neighboring cells to initiate bidirectional signaling, enabling communication between adjacent cells during development and in adult tissues.

Structure and expression: Each ephrin-B protein contains a single transmembrane domain and a cytoplasmic tail with tyrosine residues that can be phosphorylated. The C-terminal region can interact with PDZ domain-containing proteins, linking ephrin-B signaling to cytoskeletal and adhesion regulators. EFNB1 is broadly expressed with prominent roles in craniofacial development, EFNB2 is enriched in endothelial and neural tissues and influences vascular and neural processes, while EFNB3 has a more restricted expression pattern, notably in the brain and heart.

Signaling: Binding to Eph receptors triggers forward signaling in the Eph-expressing cell and reverse signaling into the ephrin-B–expressing cell. Tyrosine phosphorylation of ephrin-B by Src family kinases promotes recruitment of SH2-domain-containing adaptors and cytoskeletal regulators, modulating cell adhesion, migration, and boundary formation.

Biological roles: Ephrin-B signaling governs axon guidance, synapse formation, and neural crest cell migration, as well as vascular development and remodeling. It contributes to tissue boundary establishment during development and participates in various processes of adult tissue homeostasis and cell movement in certain contexts.

Clinical significance: Mutations in EFNB1 cause craniofrontonasal syndrome, a disorder of craniofacial development linked to altered cell movement and boundary formation. EFNB2 is essential for angiogenesis and cardiac development; EFNB3's roles are less well defined but appear important for brain development. Disruptions in ephrin-B signaling have been implicated in neurodevelopmental disorders and cancer biology.