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The Journal of Neuroscience, November 22, 2006, 26(47):12152-12164; doi:10.1523/JNEUROSCI.3072-06.2006
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Development/Plasticity/Repair
Intracellular and Trans-Synaptic Regulation of Glutamatergic Synaptogenesis by EphB Receptors
Matthew S. Kayser, Andrew C. McClelland, Ethan G. Hughes, andMatthew B. Dalva Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Correspondence should be addressed to Matthew B. Dalva, University of Pennsylvania, 1127 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104. Email: dalva{at}mail.med.upenn.edu
The majority of mature excitatory synapses in the CNS are found on dendritic spines and contain AMPA- and NMDA-type glutamate receptors apposed to presynaptic specializations. EphB receptor tyrosine kinase signaling has been implicated in both NMDA-type glutamate receptor clustering and dendritic spine formation, but it remains unclear whether EphB plays a broader role in presynaptic and postsynaptic development. Here, we find that EphB2 is involved in organizing excitatory synapses through the independent activities of particular EphB2 protein domains. We demonstrate that EphB2 controls AMPA-type glutamate receptor localization through PDZ (postsynaptic density-95/Discs large/zona occludens-1) binding domain interactions and triggers presynaptic differentiation via its ephrin binding domain. Knockdown of EphB2 in dissociated neurons results in decreased functional synaptic inputs, spines, and presynaptic specializations. Mice lacking EphB1–EphB3 have reduced numbers of synapses, and defects are rescued with postnatal reexpression of EphB2 in single neurons in brain slice. These results demonstrate that EphB2 acts to control the organization of specific classes of mature glutamatergic synapses.
Key words: Eph; ephrin; synaptogenesis; AMPA; spine; trans-synaptic
Received May 18, 2006; revised Oct. 13, 2006; accepted Oct. 13, 2006.
Correspondence should be addressed to Matthew B. Dalva, University of Pennsylvania, 1127 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104. Email: dalva{at}mail.med.upenn.edu
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