The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Presynaptic Neuronal Pentraxin Receptor Organizes Excitatory and Inhibitory Synapses
Open accessAbstract
Three neuronal pentraxins are expressed in brain, the membrane-bound “neuronal pentraxin receptor” (NPR) and the secreted proteins NP1 and NARP (i.e., NP2). Neuronal pentraxins bind to AMPARs at excitatory synapses and play important, well-documented roles in the activity-dependent regulation of neural circuits via this binding activity. However, it is unknown whether neuronal pentraxins perform roles in synapses beyond modulating postsynaptic AMPAR-dependent plasticity, and whether they may even act in inhibitory synapses. Here, we show that NPR expressed in non-neuronal cells potently induces formation of both excitatory and inhibitory postsynaptic specializations in cocultured hippocampal neurons. Knockdown of NPR in hippocampal neurons, conversely, dramatically decreased assembly and function of both excitatory and inhibitory postsynaptic specializations. Overexpression of NPR rescued the NPR knockdown phenotype but did not in itself change synapse numbers or properties. However, the NPR knockdown decreased the levels of NARP, whereas NPR overexpression produced a dramatic increase in the levels of NP1 and NARP, suggesting that NPR recruits and stabilizes NP1 and NARP on the presynaptic plasma membrane. Mechanistically, NPR acted in excitatory synapse assembly by binding to the N-terminal domain of AMPARs; antagonists of AMPA and GABA receptors selectively inhibited NPR-induced heterologous excitatory and inhibitory synapse assembly, respectively, but did not affect neurexin-1β-induced synapse assembly as a control. Our data suggest that neuronal pentraxins act as signaling complexes that function as general trans-synaptic organizers of both excitatory and inhibitory synapses by a mechanism that depends, at least in part, on the activity of the neurotransmitter receptors at these synapses. SIGNIFICANCE STATEMENT Neuronal pentraxins comprise three neuronal proteins, neuronal pentraxin receptor (NPR) which is a type-II transmembrane protein on the neuronal surface, and secreted neuronal pentraxin-1 and NARP. The general functions of neuronal pentraxins at synapses have not been explored, except for their basic AMPAR binding properties. Here, we examined the functional role of NPR at synapses because it is the only neuronal pentraxin that is anchored to the neuronal cell-surface membrane. We find that NPR is a potent inducer of both excitatory and inhibitory heterologous synapses, and that knockdown of NPR in cultured neurons decreases the density of both excitatory and inhibitory synapses. Our data suggest that NPR performs a general, previously unrecognized function as a universal organizer of synapses.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Neuronal pentraxins have been found to be involved in synapse formation and plasticity [37, 38]”
In the citing paper
“The three NPTXs interact, directly or indirectly, with the N-terminal extracellular domain of AMPAR subunits (GluA1, GluA2, GluA3 and GluA4), via their conserved pentraxin domain (Chang et al. 2010; Cho et al. 2008; Lee et al. 2017; Sia et al. 2007; Suzuki et al. 2020).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Lee et al. 2017
In the citing paper
“A potential role of NPTXR as universal organizer of both excitatory and inhibitory synapses was observed in in vitro studies (Lee et al. 2017).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Lee et al. 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
High-Efficiency Transformation of Mammalian Cells by Plasmid DNA
Chen, C., & Okayama, H. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2745 · Cited by 5,327
Neuroligin Expressed in Nonneuronal Cells Triggers Presynaptic Development in Contacting Axons
Scheiffele, P., Fan, J., Choih, J., Fetter, R., & Serafini, T. (2000) · Cell · doi:10.1016/s0092-8674(00)80877-6 · Cited by 1,218
Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms
Chen, L., Chetkovich, D. M., Petralia, R. S., Sweeney, N. T., Kawasaki, Y., Wenthold, R. J., Bredt, D. S., & Nicoll, R. A. (2000) · Nature · doi:10.1038/35050030 · Cited by 1,111
Definition of the readily releasable pool of vesicles at hippocampal synapses.
Rosenmund, C., & Stevens, C. (1996) · Neuron · doi:10.1016/s0896-6273(00)80146-4 · Cited by 1,084
Neurexins Induce Differentiation of GABA and Glutamate Postsynaptic Specializations via Neuroligins
Graf, E. R., Zhang, X., Jin, S., Linhoff, M. W., & Craig, A. M. (2004) · Cell · doi:10.1016/j.cell.2004.11.035 · Cited by 1,029
Neuroligins Determine Synapse Maturation and Function
Varoqueaux, F., Aramuni, G., Rawson, R. L., Mohrmann, R., Missler, M., Gottmann, K., Zhang, W., Südhof, T. C., & Brose, N. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.003 · Cited by 837
Self-citationα-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis
Missler, M., Zhang, W., Rohlmann, A., Kattenstroth, G., Hammer, R. E., Gottmann, K., & Südhof, T. C. (2003) · Nature · doi:10.1038/nature01755 · Cited by 699
Self-citationNeurexins: Synaptic Cell Surface Proteins Related to the α-Latrotoxin Receptor and Laminin
Ushkaryov, Y. A., Petrenko, A. G., Geppert, M., & Südhof, T. C. (1992) · Science · doi:10.1126/science.1621094 · Cited by 682
Self-citationChubykin, A. A., Atasoy, D., Etherton, M. R., Brose, N., Kavalali, E. T., Gibson, J. R., & Südhof, T. C. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.029 · Cited by 594
Self-citationSynaptic clustering of AMPA receptors by the extracellular immediate-early gene product narp.
O’Brien, R. J., Xu, D., Petralia, R. S., Steward, O., Huganir, R. L., & Worley, P. (1999) · Neuron · doi:10.1016/s0896-6273(00)80782-5 · Cited by 471
Cited by
Sorted by citations
Items 101–147 of 147
Yuan, Y., Wang, J., Huang, L., & Guo, Y. (2023) · Translational Cancer Research · doi:10.21037/tcr-22-2242 · Cited by 6
Stronger stimulus triggers synaptic transmission faster through earlier started action potential
Zhang, Z., & Huang, R. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01483-3 · Cited by 8
Guo, Z., Hong, X., Wang, X., Chen, W., & Guo, Z. (2024) · Aging Clinical and Experimental Research · doi:10.1007/s40520-023-02670-x · Cited by 5
Zhang, Y., Li, T., Miao, J., Zhang, Z., Yang, M., Wang, Z., Yang, B., Zhang, J., Li, H., Su, Q., et al. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01525 · Cited by 6
Synaptic Plasticity in the Hippocampus
Bliss, T., Collingridge, G. L., Cooke, S. F., Georgiou, J., & Morris, R. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780190065324.003.0010 · Cited by 4
mNSF: multi-sample non-negative spatial factorization
Wang, Y., Woyshner, K., Sriworarat, C., Stein-O’Brien, G., Goff, L. A., & Hansen, K. D. (2025) · Genome biology · doi:10.1186/s13059-025-03601-x · Cited by 5
Higginbotham, L. A., Carter, K., Dammer, E. B., Haque, R. U., Johnson, E. C. B., Duong, D. M., Yin, L., Jager, P. L. D., Bennett, D. A., Lah, J. J., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.22.501017 · Cited by 4
Neuhoff, S., Schmitt, L.-I., Liebig, K. C., Hezel, S., Tilahun, N. I., Kleinschnitz, C., Leo, M., & Hagenacker, T. (2025) · Biomedicines · doi:10.3390/biomedicines13081821 · Cited by 3
Shinozuka, T., Kanda, M., Sato, Y., Shimizu, D., Umeda, S., Takami, H., Hattori, N., Hayashi, M., Tanaka, C., & Kodera, Y. (2024) · Annals of Surgical Oncology · doi:10.1245/s10434-024-15353-2 · Cited by 3
Genetic Mechanisms of Experience-Dependent Neuronal Plasticity
West, A. E. (2025) · Annual Review of Genetics · doi:10.1146/annurev-genet-020325-103824 · Cited by 4
Low synaptic and neurosecretory proteins in cerebrospinal fluid in early parkinsonian disease
Jakobsson, P., Nilsson, J., Nygren, M., Zetterberg, H., Blennow, K., Constantinescu, R., Constantinescu, J., Brinkmalm, A., & Bäckström, D. C. (2025) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2025.123683 · Cited by 3
Structural dynamics in α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor gating
Gonzalez, C. U., & Jayaraman, V. (2024) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2024.102833 · Cited by 2
Leana-Sandoval, G., Kolli, A. V., Sandoval, M. A., Saavedra, E., Li, K. H., Chen, L. Y., Burlingame, A. L., Ramírez‐Franco, J., & Díaz-Alonso, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.02.626379 · Cited by 3
Rimawi, I., Yanai, S., Turgeman, G., & Yanai, J. (2023) · Scientific Reports · doi:10.1038/s41598-023-43593-x · Cited by 1
A Proteomic Study of Different Types of Diabetic Macular Edema
Shuang, W., Zhou, X., Wang, L., Yu, D., Wang, Z., & Xu, X. (2025) · Current Eye Research · doi:10.1080/02713683.2025.2516806 · Cited by 1
Göteson, A., Nilsson, J., Camporesi, E., Klahn, A. L., Hörbeck, E., Sigström, R., Jönsson, L., Sparding, T., Pålsson, E., Pelanis, A., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76187-y · Cited by 1
Zupo, L., Adinolfi, A., Pieraccioli, M., Guerra, M., Corvino, V., Ria, F., Ceci, V., Chiurchiù, V., Gaetani, L., Sperandei, S., et al. (2026) · Cell Death Discovery · doi:10.1038/s41420-026-03051-9 · Cited by 2
Muhammad, J., Siddiqui, R., & Khan, N. (2022) · Hospital Practice · doi:10.1080/21548331.2022.2088183 · Cited by 1
Kosti, A., & Bassell, G. J. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.09.029 · Cited by 1
Zhu, D., Cao, Z., Pang, X., Jiang, W., Li, C., Zhang, X., Tian, X., Tu, H., Wu, P., & Nie, H. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.875514 · Cited by 1
Souza, A. C., Golbert, D. C. F., Cassoli, J. S., Sánchez-Gendriz, I., Lima, V. V. F., da Silva, F. A. C., Martins‐de‐Souza, D., & Ribeiro, S. T. G. (2022) · Research Square · doi:10.21203/rs.3.rs-1842393/v2 · Cited by 1
Jia, X., Zhu, Q., Wu, S., Zhou, Z., & Jiang, X. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.23.590713 · Cited by 1
Begcevic, I. (2018) · TSpace (University of Toronto)
Clinical Validation of Neuronal Pentraxin Receptor as a Candidate Biomarker for Alzheimer’s Disease
Lim, B. (2020) · TSpace (University of Toronto)
Shanmugalingam, U. (2021) · Carleton University's Institutional Repository (MacOdrum Library, Carleton University) · doi:10.22215/etd/2021-14562
Nairn, A. C., & Leslie, S. N. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738571114.793579225
Souza, A. C., Golbert, D. C. F., Cassoli, J. S., Sánchez-Gendriz, I., Lima, V. V. F., da Silva, F. A. C., Martins‐de‐Souza, D., & Ribeiro, S. T. G. (2022) · Research Square · doi:10.21203/rs.3.rs-1842393/v1
Scheefhals, N. (2022) · Utrecht University Repository (Utrecht University) · doi:10.33540/1224
Zhang, H., Cicvaric, A., Bassett, T. E., Wood, E. M., Petrovic, Z., & Radulović, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00066-3
Chen, A. S., Wang, H., Li, X., Anastasaki, C., & Gutmann, D. H. (2025) · Genes & Development · doi:10.1101/gad.352508.124
Shantaraman, A., Dammer, E. B., Ugochukwu, O., Duong, D. M., Yin, L., Carter, E. K., Gearing, M., Chen-Plotkin, A., Lee, E. B., Trojanowski, J. Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26758102
Shantaraman, A., Dammer, E. B., Ugochukwu, O., Duong, D. M., Yin, L., Carter, E. K., Gearing, M., Chen-Plotkin, A., Lee, E. B., Trojanowski, J. Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26507275
Ju, L., Yang, J., Zhu, T., Liu, P., & Yang, J. (2022) · Figshare · doi:10.6084/m9.figshare.19367716
Ju, L., Yang, J., Zhu, T., Liu, P., & Yang, J. (2022) · Figshare · doi:10.6084/m9.figshare.19367719
Shantaraman, A., Dammer, E. B., Ugochukwu, O., Duong, D. M., Yin, L., Carter, E. K., Gearing, M., Chen-Plotkin, A., Lee, E. B., Trojanowski, J. Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26507230
Shantaraman, A., Dammer, E. B., Ugochukwu, O., Duong, D. M., Yin, L., Carter, E. K., Gearing, M., Chen-Plotkin, A., Lee, E. B., Trojanowski, J. Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26758099
Ju, L., Yang, J., Zhu, T., Liu, P., & Yang, J. (2022) · Figshare · doi:10.6084/m9.figshare.19367713
Backbone resonance assignment of the pentraxin domain of the neuronal pentraxin receptor (NPTXR)
Pozhidaeva, A., Li, Y., Pustovalova, Y. E., Hoch, J. C., Martinelli, D. C., Simon, B., & Hao, B. (2026) · Biomolecular NMR Assignments · doi:10.1007/s12104-025-10259-w
Etude du rôle du Syndécan à la jonction neuromusculaire de Caenorhabditis elegans
Vachon, C. (2020) · theses.fr (ABES) · doi:10.70675/4f34af1dzeed7z426dzbab2zb1e21a201491
Molecular mechanisms underlying the surface organization of the NMDA receptors during development
Bénac, N. (2024) · theses.fr (ABES) · doi:10.70675/e3508a2ezb62ez4f99zb27bz156201271974
The neuroimmune system and cognition
Klein, R. S. (2026) · Nature Immunology · doi:10.1038/s41590-026-02560-0 · Cited by 1
Leana-Sandoval, G., Sandoval, M. A., Kolli, A. V., Saavedra, E., Li, K. H., Burlingame, A. L., Ramírez‐Franco, J., & Díaz-Alonso, J. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107553
Lyndin, M., Janicot, M., Justus, M., Schiemann, P., & Wennemuth, G. (2026) · Cancer Cell International · doi:10.1186/s12935-026-04438-5
Distinct roles of AMPA receptor subunits as potential therapeutic targets in Alzheimer’s disease
Seo, J., Kim, K., & Park, M. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108394
Wu, X., Yang, L., Fan, Y., Li, X., Shi, X., Dai, C., Pang, Y., Wang, J., Cun, Y., & Dong, Z. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03831-w
Morén, J., Li, P., Bartfai, A., Günther, G., Lundkvist, Å., Bergquist, J., & Westman, G. (2026) · Scandinavian Journal of Infectious Diseases · doi:10.1080/23744235.2026.2743169
Metadata
- Authors
- Lee, S.-J., Wei, M., Zhang, C., Maxeiner, S., Pak, C., Calado Botelho, S., Trotter, J., Sterky, F. H., & Südhof, T. C.
- Affiliations
- Stanford Medicine (US)
- Peking University (CN)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-12-16
- Volume
- 37
- Issue
- 5
- Pages
- 1062-1080
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC5296791
- OpenAlex
- W2562584466
- Cited by
- 146
- References
- 36
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 28 · 2023: 13 · 2022: 18 · 2021: 21 · 2020: 21 · 2019: 6 · 2018: 9 · 2017: 9
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH052804, R37MH052804)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD078051)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- NARP, excitatory synapses, inhibitory synapses, AMPA receptors, GABA receptors, trans-synaptic signaling, postsynaptic specialization, hippocampal neurons, synaptic plasticity, presynaptic plasma membrane
- MeSH terms
- Pentraxins, Animals, C-Reactive Protein, Hippocampus, Humans, Nerve Tissue Proteins, Neurons, Receptors, Cell Surface, Synapses, Receptors, AMPA, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, GABA Antagonists, Coculture Techniques, Excitatory Postsynaptic Potentials, RNA, Small Interfering, Mice, Gene Knockdown Techniques, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
