Trans-synaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling

Andrew C. McClelland, Martin Hruska, Andrew J. Coenen, Mark Henkemeyer, Matthew B. Dalva

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8830-8835
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number19
DOIs
StatePublished - May 11 2010

Keywords

  • Cell signaling
  • Competition
  • Development
  • Ras/MAPK
  • Synaptogenesis

ASJC Scopus subject areas

  • General

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