The glutamate receptor-interacting protein family of GluR2-binding proteins is required for long-term synaptic depression expression in cerebellar Purkinje cells
Open accessAbstract
Glutamate receptor-interacting protein 1 (GRIP1) and GRIP2 are closely related proteins that bind GluR2-containing AMPA receptors and couple them to structural and signaling complexes in neurons. Cerebellar long-term synaptic depression (LTD) is a model system of synaptic plasticity that is expressed by persistent internalization of GluR2-containing AMPA receptors. Here, we show that genetic deletion of both GRIP1 and GRIP2 blocks LTD expression in primary cultures of mouse cerebellar neurons but that single deletion of either isoform allows LTD to occur. In GRIP1/2 double knock-out Purkinje cells, LTD can be fully rescued by a plasmid-driving expression of GRIP1 and partially rescued by a GRIP2 plasmid. These results indicate that the GRIP family comprises an essential molecular component for cerebellar LTD.
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Genetic deletion of GRIP1/2 or PICK1 eliminates cerebellar LTD.
“Consistent with this model, genetic deletion of GRIP1/2 or PICK1 eliminates cerebellar LTD (Takamiya et al., 2008, Steinberg et al., 2006).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Takamiya et al., 2008
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Steinberg, J. P., Takamiya, K., Shen, Y., Xia, J., Rubio, M. E., Yu, S., Jin, W., Thomas, G. M., Linden, D. J., & Huganir, R. L. (2006) · Neuron · doi:10.1016/j.neuron.2006.02.025 · Cited by 288 · cited 6× · see citing works
“In addition, mutant mice lacking the PKC isoform (Leitges et al., 2004), or PICK1 (Steinberg et al., 2006), do not express LTD.”
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AMPARs and Synaptic Plasticity: The Last 25 Years
Huganir, R. L., & Nicoll, R. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.025 · Cited by 968 · see citing works
Self-citationThe AMPA Receptor Code of Synaptic Plasticity
Diering, G. H., & Huganir, R. L. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.018 · Cited by 844 · see citing works
Self-citationRegulation of AMPA receptor trafficking and synaptic plasticity
Anggono, V., & Huganir, R. L. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.12.006 · Cited by 588 · see citing works
Self-citationSIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons
Dobbin, M. M., Madabhushi, R., Pan, L., Chen, Y., Kim, D., Gao, J., Ahanonu, B., Pao, P.-C., Qiu, Y., Zhao, Y., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3460 · Cited by 250 · see citing works
PICK1 loss of function occludes homeostatic synaptic scaling
Anggono, V., Clem, R. L., & Huganir, R. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5633-10.2011 · Cited by 111 · see citing works
Self-citationGRIP1 is required for homeostatic regulation of AMPAR trafficking
Tan, H. L., Queenan, B. N., & Huganir, R. L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512786112 · Cited by 69 · see citing works
Self-citationChapman, C. A., Nuwer, J. L., & Jacob, T. C. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.911020 · Cited by 62 · see citing works
- Authors
- Takamiya, K., Mao, L., Huganir, R. L., & Linden, D. J.
- Affiliations
- Johns Hopkins University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Linden, David J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-05-28
- Volume
- 28
- Issue
- 22
- Pages
- 5752-5755
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2587083
- OpenAlex
- W1965376953
- Cited by
- 72
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 9 · 2012: 8
- FWCI
- 2.02
- 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
- Howard Hughes Medical Institute
- National Institutes of Health (NS036715)
- Center for Neuroscience Research
- National Institute of Mental Health (R37MH051106, R37 MH51106, P50MH068830)
- National Institute of Neurological Disorders and Stroke (R01NS036715)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- GluR2, AMPA receptors, long-term depression, Purkinje cells, synaptic plasticity, receptor internalization, cerebellum
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Cerebellum, Electric Stimulation, Embryo, Mammalian, Methoxyhydroxyphenylglycol, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Purkinje Cells, Patch-Clamp Techniques, Excitatory Amino Acid Agonists, Glutamic Acid, Long-Term Synaptic Depression, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Mice, PDZ Domains
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