Presynaptic Regulation of Astroglial Excitatory Neurotransmitter Transporter GLT1

Yongjie Yang, Oguz Gozen, Andrew Watkins, Ileana Lorenzini, Angelo Lepore, Yuanzheng Gao, Svetlana Vidensky, Jean Brennan, David Poulsen, Jeong Won Park, Noo Li Jeon, Michael B. Robinson, Jeffrey D. Rothstein

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)880-894
Number of pages15
JournalNeuron
Volume61
Issue number6
DOIs
StatePublished - Mar 26 2009

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Presynaptic Regulation of Astroglial Excitatory Neurotransmitter Transporter GLT1'. Together they form a unique fingerprint.

Cite this