Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD
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Proteins that bind to the cytoplasmic tails of AMPA receptors control receptor trafficking and thus the strength of postsynaptic responses. Here we show that AP2, a clathrin adaptor complex important for endocytosis, associates with a region of GluR2 that overlaps the NSF binding site. Peptides used previously to interfere with NSF binding also antagonize GluR2-AP2 interaction. Using GluR2 mutants and peptide variants that dissociate NSF and AP2 interaction, we find that AP2 is involved specifically in NMDA receptor-induced (but not ligand-dependent) internalization of AMPA receptors, and is essential for hippocampal long-term depression (LTD). NSF function, on the other hand, is needed to maintain synaptic AMPA receptor responses, but is not directly required for NMDA receptor-mediated internalization and LTD.
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GluA2 can directly interact with AP-2 clathrin adapter complex, which allows GluA2-containing receptors to be rapidly depleted from the cell-surface.
“GluA2 can directly interact with AP-2 clathrin adapter complex, which allows GluA2-containing receptors to be rapidly depleted from the cell-surface (Kastning et al., 2007, Lee et al., 2002).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Lee et al., 2002
Cites
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588 · see citing works
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 · see citing works
Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression
Mulkey, R. M., Endo, S., Shenolikar, S., & Malenka, R. C. (1994) · Nature · doi:10.1038/369486a0 · Cited by 1,083 · see citing works
Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD
Beattie, E. C., Carroll, R. C., Yu, X., Morishita, W., Yasuda, H., von Zastrow, M., & Malenka, R. C. (2000) · Nature Neuroscience · doi:10.1038/81823 · Cited by 745 · see citing works
Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons
Passafaro, M., Piëch, V., & Sheng, M. (2001) · Nature Neuroscience · doi:10.1038/nn0901-917 · Cited by 655 · see citing works
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Borgdorff, A. J., & Choquet, D. (2002) · Nature · doi:10.1038/nature00780 · Cited by 542 · see citing works
Regulation of Synaptic Strength by Protein Phosphatase 1
Morishita, W., Connor, J. H., Xia, H., Quinlan, E. M., Shenolikar, S., & Malenka, R. C. (2001) · Neuron · doi:10.1016/s0896-6273(01)00554-2 · Cited by 227 · see citing works
Chen, H., Slepnev, V. I., Di Fiore, P. P., & De Camilli, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3257 · Cited by 138 · see citing works
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Ahmadian, G., Ju, W., Liu, L., Wyszynski, M., Lee, S. H., Dunah, A. W., Taghibiglou, C., Wang, Y., Lu, J., Wong, T. P., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600126 · Cited by 296 · see citing works
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Rao-Ruiz, P., Rotaru, D. C., van der Loo, R. J., Mansvelder, H. D., Stiedl, O., Smit, A. B., & Spijker, S. (2011) · Nature Neuroscience · doi:10.1038/nn.2907 · Cited by 192 · see citing works
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Ninan, I., Bath, K. G., Dagar, K., Perez-Castro, R., Plummer, M. R., Lee, F. S., & Chao, M. V. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1405-10.2010 · Cited by 180 · see citing works
Migues, P. V., Liu, L., Archbold, G. E. B., Einarsson, E. Ö., Wong, J., Bonasia, K., Ko, S. H., Wang, Y. T., & Hardt, O. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.3333-15.2016 · Cited by 153 · see citing works
Self-citationKastning, K., Kukhtina, V., Kittler, J. T., Chen, G., Pechstein, A., Enders, S., Lee, S. H., Sheng, M., Yan, Z., & Haucke, V. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611170104 · Cited by 88 · see citing works
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Self-citationFred, S. M., Laukkanen, L., Brunello, C. A., Vesa, L., Göös, H., Cardon, I., Moliner, R., Maritzen, T., Varjosalo, M., Casarotto, P. C., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008837 · Cited by 52 · see citing works
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- Authors
- Lee, S. H., Liu, L., Wang, Y. T., & Sheng, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of British Columbia (CA)
- Corresponding author
- Sheng, Morgan
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 36
- Issue
- 4
- Pages
- 661-674
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2018775189
- Cited by
- 441
- References
- 8
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 9 · 2018: 17 · 2017: 15 · 2016: 17 · 2015: 11 · 2014: 18 · 2013: 19 · 2012: 20
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3911 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- EJLB Foundation
- Canadian Institutes of Health Research
- National Institutes of Health (NS35050)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- AMPA receptor trafficking, GluR2, NSF, receptor internalization, synaptic plasticity, postsynaptic response
- MeSH terms
- Animals, Carrier Proteins, Cell Membrane, Endocytosis, Hippocampus, Synaptic Transmission, Neurons, Peptide Fragments, Synapses, Rats, Sprague-Dawley, Receptors, AMPA, Excitatory Amino Acid Agonists, Excitatory Postsynaptic Potentials, Protein Transport, Vesicular Transport Proteins, Adaptor Protein Complex 2, Long-Term Synaptic Depression, Rats, N-Ethylmaleimide-Sensitive Proteins
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