Cited by 160Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeuroinflammation and Neurodegeneration Mechanisms

Synaptically Targeted Narp Plays an Essential Role in the Aggregation of AMPA Receptors at Excitatory Synapses in Cultured Spinal Neurons

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O'Brien, Richard, Xu, Desheng, Mi, Ruifa, Tang, Xiaopei, Hopf, Carsten, Worley, Paul·2002·The Journal of Neuroscience

Abstract

Neuronal activity regulated pentraxin (Narp) has been implicated in the aggregation of AMPA-type glutamate receptors (GluR) at excitatory synapses. In the present paper, we examine the role of endogenous Narp in excitatory synapse formation by using novel, dominant-negative Narp mutants (dnNarp) that selectively bind endogenous Narp and prevent its accumulation at synapses. Axons from neurons transfected with wild-type Narp showed an increase in their ability to cluster AMPA receptors on spinal neurons, whereas axons from neurons transfected with dnNarp showed a marked decrease in their ability to induce GluR1 clusters on contacted dendrites. Despite their marked effect at excitatory synapses, dnNarp and wild-type Narp had no effect on the postsynaptic clustering of the inhibitory protein gephyrin or the percentage of contacts associated with staining for the presynaptic vesicle proteins GAD or synaptophysin. Use of the dnNarp mutants to suppress endogenous Narp expression by postsynaptic dendrites showed a complementary role for dendritic Narp in the clustering of synaptic AMPA receptors, as well as a reduction in the total number of excitatory synapses on transfected neurons. Together these experiments suggest an important role for Narp in the formation of excitatory synapses in cultured spinal neurons.

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Crossref · 10.1523/jneurosci.22-11-04487.2002

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Authors
O'Brien, R., Xu, D., Mi, R., Tang, X., Hopf, C., & Worley, P.
Affiliations
  • Johns Hopkins University (US)
  • Pediatrics and Genetics (US)
Venue
The Journal of Neuroscience
Published
2002-06-01
Volume
22
Issue
11
Pages
4487-4498
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2145731647
Cited by
160
References
28
Citations by year
2026: 3 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 10 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 8
FWCI
4.53
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Molecular Biology Organization
  • Johns Hopkins University
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS037694, R01NS039156)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
NARP, GluR1, excitatory synapse formation, spinal cord neurons, gephyrin, synapse number, synaptic vesicle proteins
MeSH terms
Pentraxins, Animals, C-Reactive Protein, Carrier Proteins, Cells, Cultured, Dendrites, Genes, Dominant, Humans, Kidney, Membrane Proteins, Nerve Tissue Proteins, Neurons, Receptor Aggregation, Spinal Cord, Synapses, Transfection, Immunoblotting, Gene Expression, Mutagenesis, Site-Directed, Synaptophysin, Receptors, AMPA, Macromolecular Substances, Rats

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