TY - JOUR T1 - EphrinBs Regulate <span class="sc">d</span>-Serine Synthesis and Release in Astrocytes JF - The Journal of Neuroscience JO - J. Neurosci. SP - 16015 LP - 16024 DO - 10.1523/JNEUROSCI.0481-10.2010 VL - 30 IS - 47 AU - Zhiye Zhuang AU - Bing Yang AU - Michelle H. Theus AU - Justin T. Sick AU - John R. Bethea AU - Thomas J. Sick AU - Daniel J. Liebl Y1 - 2010/11/24 UR - http://www.jneurosci.org/content/30/47/16015.abstract N2 - There is growing evidence that astrocytes play critical roles in neuron-glial interactions at the synapse. Astrocytes are believed to regulate presynaptic and postsynaptic structures and functions, in part, by the release of gliotransmitters such as glutamate, ATP, and d-serine; however, little is known of how neurons and astrocytes communicate to regulate these processes. Here, we investigated a family of transmembrane proteins called ephrinBs and Eph receptors that are expressed in the synapse and are known to regulate synaptic transmission and plasticity. In addition to their presence on CA1 hippocampal neurons, we determined that ephrins and Eph receptors are also expressed on hippocampal astrocytes. Stimulation of hippocampal astrocytes with soluble ephrinB3, known to be expressed on CA1 postsynaptic dendrites, enhanced d-serine synthesis and release in culture. Conversely, ephrinB3 had no effect on d-serine release from astrocytes deficient in EphB3 and EphA4, which are the primary receptors for ephrinB3. Eph receptors mediate this response through interactions with PICK1 (protein interacting with C-kinase) and by dephosphorylating protein kinase C α to activate the conversion of l-serine to d-serine by serine racemase. These findings are supported in vivo, where reduced d-serine levels and synaptic transmissions are observed in the absence of EphB3 and EphA4. These data support a role for ephrins and Eph receptors in regulating astrocyte gliotransmitters, which may have important implications on synaptic transmission and plasticity. ER -