Distinct roles for ephrinB3 in the formation and function of hippocampal synapses
- 8 February 2006
- journal article
- Published by Elsevier BV in Developmental Biology
- Vol. 292 (1), 34-45
- https://doi.org/10.1016/j.ydbio.2006.01.004
Abstract
The transmembrane ephrinB ligands and their Eph receptor tyrosine kinases are known to regulate excitatory synaptic functions in the hippocampus. In the CA3–CA1 synapse, ephrinB ligands are localized to the post-synaptic membrane, while their cognate Eph receptors are presumed to be pre-synaptic. Interaction of ephrinB molecules with Eph receptors leads to changes in long-term potentiation (LTP), which has been reported to be mediated by reverse signaling into the post-synaptic membrane. Here, we demonstrate that the cytoplasmic domain of ephrinB3 and hence reverse signaling is not required for ephrinB dependent learning and memory tasks or for LTP of these synapses. Consistent with previous reports, we find that ephrinB3KO null mutant mice exhibit a striking reduction in CA3–CA1 LTP that is associated with defective learning and memory tasks. We find the null mutants also show changes in both pre- and post-synaptic proteins including increased levels of synapsin and synaptobrevin and reduced levels of NMDA receptor subunits. These abnormalities are not observed in ephrinB3lacZ reverse signaling mutants that specifically delete the ephrinB3 intracellular region, supporting a cytoplasmic domain-independent forward signaling role for ephrinB3 in these processes. We also find that both ephrinB3KO and ephrinB3lacZ mice show an increased number of excitatory synapses, demonstrating a cytoplasmic-dependent reverse signaling role of ephrinB3 in regulating synapse number. Together, these data suggest that ephrinB3 may act like a receptor to transduce reverse signals to regulate the number of synapses formed in the hippocampus, and that it likely acts to stimulate forward signaling to modulate a number of other proteins involved in synaptic activity and learning/memory.This publication has 41 references indexed in Scilit:
- Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal developmentDevelopmental Biology, 2004
- Ephrin-B2 reverse signaling is required for axon pathfinding and cardiac valve formation but not early vascular developmentDevelopmental Biology, 2004
- Postsynaptic Density Assembly Is Fundamentally Different from Presynaptic Active Zone AssemblyJournal of Neuroscience, 2004
- Trans-Synaptic Eph Receptor-Ephrin Signaling in Hippocampal Mossy Fiber LTPScience, 2002
- Rapid Synaptic Remodeling by Protein Kinase C: Reciprocal Translocation of NMDA Receptors and Calcium/Calmodulin-Dependent Kinase IIJournal of Neuroscience, 2002
- EphB/Syndecan-2 Signaling in Dendritic Spine MorphogenesisNeuron, 2001
- cAMP-Dependent Protein Kinase Mediates Activity-Regulated Synaptic Targeting of NMDA ReceptorsJournal of Neuroscience, 2001
- EphB Receptors Interact with NMDA Receptors and Regulate Excitatory Synapse FormationCell, 2000
- Assembly of presynaptic active zones from cytoplasmic transport packetsNature Neuroscience, 2000
- EphrinB Ligands Recruit GRIP Family PDZ Adaptor Proteins into Raft Membrane MicrodomainsNeuron, 1999