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Publication : Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1.

First Author  Yang Y Year  2009
Journal  Neuron Volume  61
Issue  6 Pages  880-94
PubMed ID  19323997 Mgi Jnum  J:147349
Mgi Id  MGI:3840375 Doi  10.1016/j.neuron.2009.02.010
Citation  Yang Y, et al. (2009) Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron 61(6):880-94
abstractText  The neuron-astrocyte synaptic complex is a fundamental operational unit of the nervous system. Astroglia regulate synaptic glutamate, via neurotransmitter transport by GLT1/EAAT2. Astroglial mechanisms underlying this essential neuron-glial communication are not known. We now show that presynaptic terminals regulate astroglial synaptic functions, GLT1/EAAT2, via kappa B-motif binding phosphoprotein (KBBP), the mouse homolog of human heterogeneous nuclear ribonucleoprotein K (hnRNP K), which binds the GLT1/EAAT2 promoter. Neuron-stimulated KBBP is required for GLT1/EAAT2 transcriptional activation and is responsible for astroglial alterations in neural injury. Denervation of neuron-astrocyte signaling by corticospinal tract transection, ricin-induced motor neuron death, or neurodegeneration in amyotrophic lateral sclerosis all result in reduced astroglial KBBP expression and transcriptional dysfunction of astroglial transporter expression. Presynaptic elements dynamically coordinate normal astroglial function and also provide a fundamental signaling mechanism by which altered neuronal function and injury leads to dysregulated astroglia in CNS disease.
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