Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product narp.
Open accessAbstract
Narp (neuronal activity-regulated pentraxin) is a secreted immediate-early gene (IEG) regulated by synaptic activity in brain. In this study, we demonstrate that Narp possesses several properties that make it likely to play a key role in excitatory synaptogenesis. Narp is shown to be selectively enriched at excitatory synapses on neurons from both the hippocampus and spinal cord. Overexpression of recombinant Narp increases the number of excitatory but not inhibitory synapses in cultured spinal neurons. In transfected HEK 293T cells, Narp interacts with itself, forming large surface clusters that coaggregate AMPA receptor subunits. Moreover, Narp-expressing HEK 293T cells can induce the aggregation of neuronal AMPA receptors. These studies support a model in which Narp functions as an extracellular aggregating factor for AMPA receptors.
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Narp can interact with the N-terminal domain of AMPA receptors localized extracellularly and facilitate AMPA receptor clustering at both the pre- and post-synaptic cell in response to stimulation.
“Narp can interact with the N-terminal domain of AMPA receptors localized extracellularly and facilitate AMPA receptor clustering at both the pre- and post-synaptic cell in response to stimulation (O’Brien et al., 1999).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as O’Brien et al., 1999
During development, sensory stimuli can activate Narp expression which promotes PV interneuron excitation, leading to feed-forward inhibition.
“This suggests that during development, sensory stimuli can activate Narp expression which promotes PV interneuron excitation, leading to feed-forward inhibition (O’Brien et al., 1999; Gu et al., 2013).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as O’Brien et al., 1999
NPTX2 is released from the pre-synaptic terminal in response to neuronal activity, seizure, long-term potentiation, or BDNF.
“It is released from the pre-synaptic terminal in response to neuronal activity, seizure (O’Brien et al. 1999), long-term potentiation (LTP) (Tsui et al. 1996) or brain-derived neurotrophic factor (BDNF) (Mariga et al. 2015).”
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. 1999
The NPTX complex promotes AMPAR aggregation and stabilisation.
“In particular, the complex promotes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) aggregation and stabilisation (O’Brien et al. 1999)”
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. 1999
NPTXs regulate circuit rhythmogenesis and integration by controlling expression and synaptic localization of AMPAR and coordination of excitatory synapses maturation onto PV interneurons.
“NPTXs regulate circuit rhythmogenesis and integration by controlling expression and synaptic localization of AMPAR and coordination of excitatory synapses maturation onto PV interneurons (O’Brien et al. 1999; Pelkey et al. 2015).”
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. 1999
NPTX heterocomplex plays a dual role in synapse formation and depression.
“In addition, NPTX heterocomplex play a dual role in synapse formation and depression.”
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. 1999
NPTX2 is released from the pre-synaptic terminal in response to seizures.
“NPTX2 was initially discovered to be released from the pre-synaptic terminal in response to seizures (O’Brien et al. 1999).”
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. 1999
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- Authors
- O’Brien, R. J., Xu, D., Petralia, R. S., Steward, O., Huganir, R. L., & Worley, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- National Institutes of Health (US)
- University of Virginia (US)
- Corresponding author
- Worley, Paul
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 23
- Issue
- 2
- Pages
- 309-323
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2064751454
- Cited by
- 471
- References
- 61
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 15 · 2023: 8 · 2022: 12 · 2021: 23 · 2020: 15 · 2019: 9 · 2018: 11 · 2017: 21 · 2016: 8 · 2015: 14 · 2014: 17 · 2013: 13 · 2012: 22
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ns001652-02)
- National Institute of Mental Health (R01MH053608, R01MH53608)
- National Institute of Neurological Disorders and Stroke (R01NS036715, K08 NS01652, R01NS36715)
- 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, synaptic clustering, immediate early genes, hippocampus, spinal cord neurons
- MeSH terms
- Pentraxins, Animals, Axons, C-Reactive Protein, Cell Line, Cells, Cultured, Dendrites, Extracellular Space, Hippocampus, Immunohistochemistry, Microscopy, Electron, Nerve Tissue Proteins, Neurons, Spinal Cord, Synapses, Transfection, Blotting, Western, Rats, Sprague-Dawley, Immediate-Early Proteins, Receptors, AMPA, Rats
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