Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD
Abstract
Long-term depression (LTD) can be induced at hippocampal CA1 synapses by activation of either NMDA receptors (NMDARs) or group I metabotropic glutamate receptors (mGluRs), using their selective agonists NMDA and (RS)-3,5-dihydroxyphenylglycine (DHPG), respectively. Recent studies revealed that DHPG-LTD is dependent on activation of postsynaptic protein tyrosine phosphatases (PTPs), which transiently dephosphorylate tyrosine residues in AMPA receptors (AMPARs). Here we show that while both endogenous GluR2 and GluR3 AMPAR subunits are tyrosine phosphorylated at basal activity, only GluR2 is dephosphorylated in DHPG-LTD. The tyrosine dephosphorylation of GluR2 does not occur in NMDA-LTD. Conversely, while NMDA-LTD is associated with the dephosphorylation of GluR1-serine-845, DHPG-LTD does not alter the phosphorylation of this site. The increased AMPAR endocytosis in DHPG-LTD is PTP-dependent and involves tyrosine dephosphorylation of cell surface AMPARs. Together, these results indicate that the subunit selective tyrosine dephosphorylation of surface GluR2 regulates AMPAR internalisation in DHPG-LTD but not in NMDA-LTD in the hippocampus.
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Hippocampal mGluR-mediated LTD involves dephosphorylation of GluA2 Y876 and is completely blocked by inhibitors of tyrosine phosphatases.
“Interestingly, hippocampal mGluR-mediated LTD involves the dephosphorylation of GluA2 Y876 and is completely blocked by inhibitors of tyrosine phosphatases (Moult et al., 2006, Gladding et al., 2009).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Gladding et al., 2009
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References 69 · Cited by 74
- Authors
- Gladding, C. M., Collett, V. J., Jia, Z., Bashir, Z. I., Collingridge, G. L., & Molnár, E.
- Affiliations
- University of Bristol (GB)
- University of Toronto (CA)
- Corresponding author
- Molnár, Elek
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 40
- Issue
- 2
- Pages
- 267-279
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2010939168
- Cited by
- 74
- References
- 69
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Wellcome Trust
- Canadian Institutes of Health Research
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/F011326/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- tyrosine dephosphorylation, AMPA receptor endocytosis, metabotropic glutamate receptors, group I mGluRs, NMDA receptor, protein tyrosine phosphatase, GluR2 subunit, hippocampal CA1 synapses, synaptic plasticity
- MeSH terms
- Amino Acid Sequence, Animals, Endocytosis, Female, Glycine, Hippocampus, Molecular Sequence Data, Phosphorylation, Resorcinols, Synapses, Tyrosine, N-Methylaspartate, Sequence Alignment, Rats, Wistar, Receptors, AMPA, Receptors, Metabotropic Glutamate, Excitatory Amino Acid Agonists, Protein Subunits, Long-Term Synaptic Depression, Rats
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