hide
Free keywords:
6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
Animals
Animals, Newborn
Biotinylation/methods
Carrier Proteins/genetics/metabolism
Cells, Cultured
Embryo, Mammalian
Endocytosis/drug effects/genetics
Ephrin-B2/deficiency/*metabolism
Excitatory Amino Acid Agonists/pharmacology
Excitatory Amino Acid Antagonists/pharmacology
Excitatory Postsynaptic Potentials/drug effects/genetics
Hippocampus/cytology
Immunoprecipitation/methods
Intracellular Signaling Peptides and Proteins
Mice
Mice, Knockout
Nerve Tissue Proteins/genetics/metabolism
Neurons/cytology/drug effects/*metabolism
Patch-Clamp Techniques
Phosphorylation/drug effects
Protein Transport/drug effects/genetics
Rats
Rats, Wistar
Receptors, AMPA/genetics/*metabolism
Serine/*metabolism
Signal Transduction/drug effects/physiology
Synapses/drug effects/*metabolism
Synaptic Transmission/drug effects/physiology
Transfection/methods
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
Abstract:
Plasticity in the brain is essential for maintaining memory and learning and is associated with the dynamic membrane trafficking of AMPA receptors. EphrinB proteins, ligands for EphB receptor tyrosine kinases, are transmembrane molecules with signaling capabilities that are required for spine morphogenesis, synapse formation and synaptic plasticity. Here, we describe a molecular mechanism for ephrinB2 function in controlling synaptic transmission. EphrinB2 signaling is critical for the stabilization of AMPA receptors at the cellular membrane. Mouse hippocampal neurons from conditional ephrinB2 knockouts showed enhanced constitutive internalization of AMPA receptors and reduced synaptic transmission. Mechanistically, glutamate receptor interacting proteins bridge ephrinB ligands and AMPA receptors. Moreover, this function involved a regulatory aspect of ephrinB reverse signaling that involves the phosphorylation of a single serine residue in their cytoplasmic tails. In summary, our findings uncover a model of cooperative AMPA receptor and ephrinB reverse signaling at the synapse.
