ephrinB3

Ephrin-B3, also known as EFNB3, is a transmembrane ligand of the ephrin family that binds Eph receptor tyrosine kinases on adjacent cells. Like other ephrin-B proteins, ephrin-B3 participates in bidirectional signaling, enabling communication across neighboring cells during development and in adult tissue.

Molecularly, ephrin-B3 contains an extracellular ephrin domain that engages EphB receptors, a single transmembrane segment, and a cytoplasmic tail with motifs that propagate intracellular signals, including a PDZ-binding motif that recruits scaffolding and signaling proteins. Engagement with Eph receptors can trigger forward signaling in the Eph receptor–expressing cell and reverse signaling in the ephrin-expressing cell, allowing coordinated responses such as changes in adhesion, cytoskeletal organization, and cell movement.

Expression and roles: EFNB3 is expressed in the developing and adult nervous system, with notable presence in brain regions such as the cortex and hippocampus. It participates in axon guidance, neuronal migration, and synapse formation, contributing to the organization of neural circuits. It may influence dendritic spine maturation and synaptic plasticity, and can affect cell adhesion and cytoskeletal dynamics through bidirectional signaling pathways.

Regulation and interactions: Ephrin-B3 signaling is modulated by phosphorylation on its cytoplasmic tail and interactions with Src-family kinases and PDZ-domain proteins. It interacts with various EphB receptors on neighboring cells, and its activity can be regulated by neuronal activity and developmental cues.

Clinical relevance: In humans, variations in EFNB3 and altered ephrin-B3 signaling have been examined in the context of neurodevelopmental processes and brain function in animal models; associations with specific human diseases remain under investigation and are not yet established.