ephrinB1

Ephrin-B1, or EFNB1, is a member of the ephrin family of membrane-bound ligands that activate Eph receptor tyrosine kinases. It is a class B ephrin, characterized by a single-pass transmembrane topology, an extracellular ephrin domain, and a cytoplasmic tail that contains a PDZ-binding motif. The EFNB1 gene encodes the human ephrin-B1 protein.

Ephrin-B1 interacts with EphB receptors on neighboring cells to elicit bidirectional signaling. Forward signaling occurs in the EphB-expressing cell after receptor activation, promoting changes in cell adhesion, migration, and cytoskeletal organization. Reverse signaling occurs in the ephrin-B1–expressing cell through phosphorylation of its cytoplasmic tail by Src family kinases and recruitment of PDZ-domain proteins, resulting in downstream regulation of Rho family GTPases and actin dynamics. These signaling events influence tissue patterning and boundary formation during development.

Biological roles: Ephrin-B1 participates in axon pathfinding, neuronal migration, and synaptic maturation in the nervous system, as well as vascular patterning and craniofacial development. Its expression is dynamic, with prominent activity during embryogenesis and in certain adult tissues.

Clinical significance: Mutations in EFNB1 cause craniofrontonasal syndrome (CFNS), an X-linked craniofacial disorder. The phenotype is often more pronounced in females due to mosaic expression from X-inactivation. Research into EFNB1 helps illuminate mechanisms of neural crest migration, craniofacial morphogenesis, and synaptic connectivity.

Expression and regulation: EFNB1 is expressed broadly in developing tissues, with notable activity in the nervous system, craniofacial regions, and vasculature. Its signaling is modulated by phosphorylation and interactions with PDZ-domain proteins, enabling context-dependent responses.