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Cited by 237Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismNeuroinflammation and Neurodegeneration Mechanisms

Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1

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Yang, Yongjie, Gozen, Oguz, Watkins, Andrew, Lorenzini, Ileana, Lepore, Angelo, Gao, Yuanzheng, Vidensky, Svetlana, Brennan, Jean +5 more·2009·Neuron
DOI 10.1016/j.neuron.2009.02.010PMC PMC2743171
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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.

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Authors
Yang, Y., Gozen, O., Watkins, A., Lorenzini, I., Lepore, A., Gao, Y., Vidensky, S., Brennan, J., Poulsen, D., Won Park, J., Li Jeon, N., Robinson, M. B., & Rothstein, J. D.
Affiliations
  • Johns Hopkins University (US)
  • University of Montana (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Rothstein, Jeffrey D.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2009-03
Volume
61
Issue
6
Pages
880-894
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2009.02.010
PMC
PMC2743171
OpenAlex
W2005864274
Cited by
237
References
2
Citations by year
2026: 6 · 2025: 7 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 20 · 2018: 11 · 2017: 11 · 2016: 14 · 2015: 20 · 2014: 23 · 2013: 16 · 2012: 18
FWCI
9.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (T32EY017203)
  • National Institute of Neurological Disorders and Stroke (NS 33958, R01NS036465, R01NS052179, NS 36465, R01NS033958)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
presynaptic modulation, hnRNP K, transcriptional regulation, glutamate uptake, amyotrophic lateral sclerosis, neurodegeneration
MeSH terms
Analysis of Variance, Animals, Animals, Newborn, Astrocytes, Cerebral Cortex, Dose-Response Relationship, Drug, Embryo, Mammalian, Humans, Kainic Acid, Mice, Inbred C57BL, Mice, Transgenic, Nerve Degeneration, Neurons, Pyramidal Tracts, Spinal Cord Injuries, Superoxide Dismutase, Synapses, Tetrodotoxin, Transfection, Up-Regulation, Mutagenesis, NF-kappa B, Rats, Sprague-Dawley, Presynaptic Terminals, Excitatory Amino Acid Agents, Coculture Techniques, Electrophoretic Mobility Shift Assay, Sodium Channel Blockers, Excitatory Amino Acid Transporter 2, Microfluidic Analytical Techniques, Green Fluorescent Proteins, Mice, Rats

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