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Published Online December 20, 2001
Science DOI: 10.1126/science.1065983

Reports

Submitted on September 4, 2001
Accepted on November 27, 2001

Modulation of NMDA Receptor-Dependent Calcium Influx and Gene Expression Through EphB Receptors

Mari A. Takasu 1, Matthew B. Dalva 1, Richard E. Zigmond 2, Michael E. Greenberg 1*

1 Division of Neuroscience, Children's Hospital, and the Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2 Department of Neurobiology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Division of Neuroscience, Children's Hospital, and the Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: michael.greenberg{at}tch.harvard.edu.

Protein-protein interactions and calcium entry through the N-methyl-D-aspartate (NMDA)-type glutamate receptor regulate synaptic development and plasticity in the central nervous system. The EphB receptor tyrosine kinases are localized at excitatory synapses where they cluster and associate with NMDA receptors. We identified a mechanism whereby EphBs modulate NMDA receptor function. EphrinB2 activation of EphB in primary cortical neurons potentiates NMDA receptor-dependent influx of calcium. Treatment of cells with EphrinB2 led to NMDA receptor tyrosine phosphorylation through activation of the Src family of tyrosine kinases. These ephrinB2-dependent events result in enhanced NMDA receptor-dependent gene expression. These findings indicate that ephrinB2 stimulation of EphB modulates the functional consequences of NMDA receptor activation and suggest a mechanism whereby activity-independent and activity-dependent signals converge to regulate the development and remodeling of synaptic connections.


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