Coordinating Synaptic Development

Two different mechanisms guide the development of the central nervous system. Molecular signals initially guide developing neurons to the correct position and, once neuronal activity begins, repeated stimulation helps synapses form and mature. Takasu et al. (see the Perspective by Ghosh) describe a signaling mechanism that may integrate these two processes. Ephrins and their receptors are cell-surface proteins that participate in interactions of developing axons and dendrites that are largely independent of neuronal activity. However, the activation of the EphB subtype of ephrin receptors in rat neurons potentiated signaling by N-methyl-D-aspartate (NMDA)-type glutamate receptors, which mediate activity-dependent effects on developing neurons. Activated EphB proteins were associated physically with NMDA receptors and caused the activation of the Src tyrosine kinase, which apparently phosphorylates the NMDA receptor and thus modulates activity-dependent control of neuronal gene expression. M. A. Takasu, M. B. Dalva, R. E. Zigmond, M. E. Greenberg, Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors. Science 295, 491-495 (2002). [Abstract] [Full Text] A. Ghosh, Learning more about NMDA receptor regulation. Science 295, 449-450 (2002). [Full Text]