Trans-synaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling.
Nervous system function requires tight control over the number of synapses individual neurons receive, but the underlying cellular and molecular mechanisms that regulate synapse number remain obscure. Here we present evidence that a trans-synaptic interaction between EphB2 in the presynaptic compartment and ephrin-B3 in the postsynaptic compartment regulates synapse density and the formation of dendritic spines. Observations in cultured cortical neurons demonstrate that synapse density scales with ephrin-B3 expression level and is controlled by ephrin-B3-dependent competitive cell-cell interactions. RNA interference and biochemical experiments support the model that ephrin-B3 regulates synapse density by directly binding to Erk1/2 to inhibit postsynaptic Ras/mitogen-activated protein kinase signaling. Together these findings define a mechanism that contributes to synapse maturation and controls the number of excitatory synaptic inputs received by individual neurons.
McClelland
Andrew C
AC
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Hruska
Martin
M
Coenen
Andrew J
AJ
Henkemeyer
Mark
M
Dalva
Matthew B
MB
D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D049229:Dendritic Spines / Q000378:metabolism; D036388:Ephrin-B2 / Q000378:metabolism*; D036389:Ephrin-B3 / Q000172:deficiency / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008024:Ligands; D020935:MAP Kinase Signaling System; D051379:Mice; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013569:Synapses / Q000201:enzymology*
D036388:Ephrin-B2; D036389:Ephrin-B3; D008024:Ligands; D048049:Extracellular Signal-Regulated MAP Kinases
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