Synaptically Targeted Narp Plays an Essential Role in the Aggregation of AMPA Receptors at Excitatory Synapses in Cultured Spinal Neurons
Open accessAbstract
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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NPTXs participate in synaptic plasticity.
“Among the latter, neuronal pentraxins (NPTXs) have gained attention as they participate in synaptic plasticity (O’Brien et al. 2002, 1999; Sia et al. 2007; Xu et al. 2003)”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as O’Brien et al. 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
- Publisher
- Society for Neuroscience
- Published
- 2002-06-01
- Volume
- 22
- Issue
- 11
- Pages
- 4487-4498
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758786
- 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
- bronze
- doi.org
- 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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