Bidirectional ephrin/Eph signaling in synaptic functions

Abstract

Eph receptors, the largest family of receptor tyrosine kinases, and their membrane bound ligands, the ephrins, are involved in multiple developmental and adult processes within and outside of the nervous system. Bi-directional signaling from both the receptor and the ligand is initiated by ephrin-Eph binding upon cell-cell contact, and involves interactions with distinct subsets of downstream signaling molecules related to specific functions. In the CNS, Ephs and ephrins act as attractive/repulsive, migratory and cell adhesive cues during development and participate in synaptic functions in adult animals. In this review, we will focus on recent findings highlighting the functions of ephrin/Eph signaling in dendritic spine morphogenesis, synapse formation and synaptic plasticity.

Figure 1

Schematic drawing of the ephrin and Eph domain structures and summary of protein interactions involved in forward and reverse signaling. Discrete functional domains are labeled in red and interacting proteins are labeled in black. ↔ with solid line depicts established interactions while ↔ with dashed line depicts predicted interactions.

Figure 2

Localization and signaling directionality of ephrins and Ephs in different regions of the mammalian hippocampus.