The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD
Open accessAbstract
The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors is subject to functionally distinct constitutive and regulated clathrin-dependent endocytosis, contributing to various forms of synaptic plasticity. In HEK293 cells transiently expressing GluR1 or GluR2 mutants containing domain deletions or point mutations in their intracellular carboxyl termini (CT), we found that deletion of the first 10 amino acids (834-843) selectively reduced the rate of constitutive AMPA receptor endocytosis, whereas truncation of the last 15 amino acids of the GluR2 CT, or point mutation of the tyrosine residues in this region, only eliminated the regulated (insulin-stimulated) endocytosis. Moreover, in hippocampal slices, both insulin treatment and low-frequency stimulation (LFS) specifically stimulated tyrosine phosphorylation of the GluR2 subunits of native AMPA receptors, and the enhanced phosphorylation appears necessary for both insulin- and LFS-induced long-term depression of AMPA receptor-mediated excitatory postsynaptic currents. Thus, our results demonstrate that constitutive and regulated AMPA receptor endocytosis requires different sequences within GluR CTs and tyrosine phosphorylation of GluR2 CT is required for the regulated AMPA receptor endocytosis and hence the expression of certain forms of synaptic plasticity.
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“Multiple studies have shown both in slice physiology experiments and in vivo that treatment with a short peptide mimicking the tyrosine-rich region of GluA2 (called the 3Y peptide) completely blocks LTD as well as activity-dependent GluA2 endocytosis (Fox et al., 2007, Ahmadian et al., 2004), while having no effect on basal synaptic transmission.”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Ahmadian et al., 2004
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“Thus the “slot hypothesis” offers some explanation for the prominent role of GluA1 in LTP and of GluA2 in LTD, via the rapid activity-dependent mobilization of GluA1-containing receptors onto the cell surface during LTP, and the removal of GluA2 containing receptors from the cell-surface during LTD through interactions with AP2 and/or through interactions involving the GluA2 Y-rich motif (Ahmadian”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Ahmadian et al., 2004
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Hollmann, M., & Heinemann, S. F. (1994) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.17.030194.000335 · Cited by 4,056
Hayashi, Y., Shi, S.-H., Esteban, J. A., Piccini, A., Poncer, J.-C., & Malinow, R. (2000) · Science · doi:10.1126/science.287.5461.2262 · Cited by 1,524
Reinsertion or Degradation of AMPA Receptors Determined by Activity-Dependent Endocytic Sorting
Ehlers, M. D. (2000) · Neuron · doi:10.1016/s0896-6273(00)00129-x · Cited by 1,096
A peptide carrier for the delivery of biologically active proteins into mammalian cells
Morris, M. C., Depollier, J., Méry, J., Heitz, F., & Divita, G. (2001) · Nature Biotechnology · doi:10.1038/nbt1201-1173 · Cited by 1,019
Lu, W.-Y., Man, H., Ju, W. H., Trimble, W. S., MacDonald, J. F., & Wang, Y. T. (2001) · Neuron · doi:10.1016/s0896-6273(01)00194-5 · Cited by 935
Self-citationEvidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons
Wenthold, R., Petralia, R., Blahos J, II, & Niedzielski, A. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-06-01982.1996 · Cited by 850
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
Man, H., Lin, J., Ju, W. H., Ahmadian, G., Liu, L., Becker, L. E., Sheng, M., & Wang, Y. T. (2000) · Neuron · doi:10.1016/s0896-6273(00)81067-3 · Cited by 711
Self-citationRole of AMPA Receptor Cycling in Synaptic Transmission and Plasticity
Lüscher, C., Xia, H., Beattie, E. C., Carroll, R. C., von Zastrow, M., Malenka, R. C., & Nicoll, R. A. (1999) · Neuron · doi:10.1016/s0896-6273(00)81119-8 · Cited by 692
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
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Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
PDZ domain proteins of synapses
Kim, E., & Sheng, M. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1517 · Cited by 1,630
Self-citationReceptor trafficking and synaptic plasticity
Collingridge, G. L., Isaac, J. T. R., & Wang, Y. T. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1556 · Cited by 1,046
Self-citationSynaptic AMPA receptor plasticity and behavior
Kessels, H. W., & Malinow, R. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.015 · Cited by 993
Long-term depression in the CNS
Collingridge, G. L., Peineau, S., Howland, J. G., & Wang, Y. T. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2867 · Cited by 926
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Metadata
- Authors
- Ahmadian, G., Ju, W., Liu, L., Wyszynski, M., Lee, S. H., Dunah, A. W., Taghibiglou, C., Wang, Y., Lu, J., Wong, T. P., Sheng, M., & Wang, Y. T.
- Affiliations
- National Institute of Genetic Engineering and Biotechnology (IR)
- University of British Columbia (CA)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wang, Yu Tian
- ORCID
- Venue
- The EMBO Journal
- Published
- 2004-02-19
- Volume
- 23
- Issue
- 5
- Pages
- 1040-1050
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC380981
- OpenAlex
- W2141680511
- Cited by
- 296
- References
- 28
- Citations by year
- 2026: 8 · 2025: 2 · 2024: 9 · 2023: 3 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 14 · 2018: 18 · 2017: 9 · 2016: 14 · 2015: 11 · 2014: 16 · 2013: 25 · 2012: 18
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Neurological Disorders and Stroke (NS 35050, R01NS035050)
- 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 receptors, GluR2, tyrosine phosphorylation, receptor internalization, insulin signaling, long-term depression, clathrin-mediated endocytosis, carboxyl terminus, low-frequency stimulation, synaptic plasticity, excitatory postsynaptic currents, hippocampus
- MeSH terms
- Aging, Amino Acid Sequence, Animals, Cells, Cultured, Endocytosis, Hippocampus, Humans, Insulin, Molecular Sequence Data, Mutation, Synaptic Transmission, Neurons, Phosphorylation, Time Factors, Sequence Alignment, Rats, Sprague-Dawley, Receptors, AMPA, Phosphotyrosine, Protein Subunits, Long-Term Synaptic Depression, Rats, In Vitro Techniques
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