GRIP1 is required for homeostatic regulation of AMPAR trafficking
Open accessAbstract
Significance: Homeostatic plasticity constrains neuronal networks, allowing the brain to maintain a dynamic equilibrium. Loss of homeostatic plasticity disrupts normal brain function and has been implicated in autism spectrum disorder. Much of homeostatic regulation centers on synapses. In particular, excitatory AMPA-type glutamate receptors (AMPARs) are moved in and out of synapses to recalibrate neuronal activity. AMPARs can be inserted at the surface to compensate for inactivity or removed to compensate for hyperactivity. We found that GRIP1, an AMPAR-binding protein implicated in autism, regulates the homeostatic shuttling of AMPARs between cytoplasmic and synaptic pools. Restoring GRIP1 regulation may therefore prove therapeutically useful in autism.
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Bicuculline-induced scaling-down in cultured neurons involves the downregulation of GluA1/2/3 protein levels as well as a reduced synaptic targeting of all AMPAR subunits.
“Bicuculline-induced scaling-down in cultured neurons involves the downregulation of GluA1/2/3 protein levels as well a reduced synaptic targeting of all AMPAR subunits (Diering et al., 2014, Tan et al., 2015).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Tan et al., 2015
The ‘Inactivity-Induced Synaptic Scaling Is Blocked in GRIP Knockout’ section reports that bicuculline reduced total GluA1, GluA2, and GluA3 expression and reduced surface levels of all three in cultured neurons (Fig. S1; Fig. 3 A–D). It does not establish reduced synaptic targeting of each subunit specifically; the reported subunit-specific measurements are of surface levels. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTTX-induced homeostatic scaling-up in cultured neurons increases GluA1 protein expression as well as surface and synaptic levels of CP-AMPARs (GluA1 homomers) and GluA1/2 heteromers, but not GluA3-containing AMPARs.
“TTX-induced homeostatic scaling-up in cultured neurons increases GluA1 protein expression as well as surface and synaptic levels of CP-AMPARs (GluA1 homomers) and GluA1/2 heteromers but not in GluA3-containing AMPARs (Figure 3) (Diering et al., 2014, Soares et al., 2013, Tan et al., 2015, Kim and Ziff, 2014, Hu et al., 2010).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Tan et al., 2015
The Results section reports that chronic TTX increased total GluA1 and surface GluA1 and GluA2, but not surface GluA3. The Discussion interprets the surface changes as preferential GluA1/GluA2 heteromer insertion. It does not establish increased surface or synaptic GluA1-homomer CP-AMPARs; instead, it says their synaptic insertion was unlikely to predominate (page numbers unavailable). (LLM, conf=0.88)
Experimental — accuracy not yet measuredDuring scaling-down, GRIP1 protein is upregulated but remains in intracellular compartments where it may act to sequester internalized GluA2-containing receptors away from the synapse.
“Concomitantly, GRIP1 protein is upregulated during scaling-down, but remains in intracellular compartments where it may act to sequester internalized GluA2-containing receptors away from the synapse (Figure 3) (Tan et al., 2015).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Tan et al., 2015
The section on GRIP1 subcellular distribution (Fig. 4) reports that scaling down increases cytoplasmic GRIP1 and decreases synaptic GRIP1. It describes a cytoplasmic GRIP1 pool that can retain AMPARs intracellularly, but does not show that the increased pool sequesters internalized GluA2-containing receptors during scaling down; it instead reports reduced overall GRIP1–GluA2 interaction. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDeletion of the GRIP1/2 genes completely blocks scaling-up.
“Consistent with these data, deletion of the GRIP1/2 genes completely blocks scaling-up (Tan et al., 2015).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Tan et al., 2015
Neither GRIP1/2 nor PICK1 are required for scaling-down.
“Neither GRIP1/2 nor PICK1 are required for scaling-down (Tan et al., 2015, Anggono et al., 2011).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Tan et al., 2015
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Cites
Synaptic scaling mediated by glial TNF-α
Stellwagen, D., & Malenka, R. C. (2006) · Nature · doi:10.1038/nature04671 · Cited by 1,715 · see citing works
The self-tuning neuron: synaptic scaling of excitatory synapses
Turrigiano, G. G. (2008) · Cell · doi:10.1016/j.cell.2008.10.008 · Cited by 1,533 · see citing works
Synaptic plasticity, memory and the hippocampus: a neural network approach to causality
Neves, G., Cooke, S. F., & Bliss, T. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2303 · Cited by 1,207 · see citing works
The cell biology of synaptic plasticity: AMPA receptor trafficking
Shepherd, J. D., & Huganir, R. L. (2007) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123516 · Cited by 978 · see citing works
Self-citationAMPARs 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-citationGRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors
Dong, H., O’Brien, R., Fung, E. T., Lanahan, A. A., Worley, P. F., & Huganir, R. L. (1997) · Nature · doi:10.1038/386279a0 · Cited by 871 · see citing works
Self-citationArc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors
Shepherd, J. D., Rumbaugh, G., Wu, J., Chowdhury, S., Plath, N., Kuhl, D., Huganir, R. L., & Worley, P. F. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.034 · Cited by 779 · see citing works
Self-citationActivity-Dependent Modulation of Synaptic AMPA Receptor Accumulation
O’Brien, R. J., Kamboj, S., Ehlers, M. D., Rosen, K. R., Fischbach, G. D., & Huganir, R. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80624-8 · Cited by 688 · see citing works
Self-citationBourgeron, T. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.06.003 · Cited by 637 · cited 1× · see citing works
“Autism spectrum disorders (ASD) are associated with abnormal synaptogenesis and imbalance between excitatory and inhibitory currents (3, 45).”
BackgroundSutton, M. A., Ito, H. T., Cressy, P., Kempf, C., Woo, J. C., & Schuman, E. M. (2006) · Cell · doi:10.1016/j.cell.2006.03.040 · Cited by 633 · see citing works
Regulation 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-citationActivity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors
Ju, W. H., Morishita, W., Tsui, J., Gaietta, G. M., Deerinck, T. J., Adams, S., Garner, C. C., Tsien, R. Y., Ellisman, M. H., & Malenka, R. C. (2004) · Nature Neuroscience · doi:10.1038/nn1189 · Cited by 524 · see citing works
Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites
Setou, M., Seog, D., Tanaka, Y., Kanai, Y., Takei, Y., Kawagishi, M., & Hirokawa, N. (2002) · Nature · doi:10.1038/nature743 · Cited by 518 · see citing works
Adaptation to Synaptic Inactivity in Hippocampal Neurons
Thiagarajan, T. C., Lindskog, M., & Tsien, R. W. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.037 · Cited by 482 · see citing works
Synaptic Signaling by All-Trans Retinoic Acid in Homeostatic Synaptic Plasticity
Aoto, J., Nam, C. I., Poon, M. M., Ting, P., & Chen, L. (2008) · Neuron · doi:10.1016/j.neuron.2008.08.012 · Cited by 397 · see citing works
Novel Anchorage of GluR2/3 to the Postsynaptic Density by the AMPA Receptor–Binding Protein ABP
Srivastava, S., Osten, P., Vilim, F. S., Khatri, L., Inman, G. J., States, B. A., Daly, C., deSouza, S., Abagyan, R. A., Valtschanoff, J. G., et al. (1998) · Neuron · doi:10.1016/s0896-6273(00)80568-1 · Cited by 357 · see citing works
Synaptic Scaling and Homeostatic Plasticity in the Mouse Visual Cortex In Vivo
Keck, T., Keller, G. B., Jacobsen, R. I., Eysel, U. T., Bonhoeffer, T., & Hübener, M. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.018 · Cited by 357 · see citing works
Daw, M. I., Chittajallu, R., Bortolotto, Z. A., Dev, K. K., Duprat, F., Henley, J. M., Collingridge, G. L., & Isaac, J. T. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00160-4 · Cited by 318 · see citing works
Postsynaptic expression of homeostatic plasticity at neocortical synapses
Wierenga, C. J., Ibata, K., & Turrigiano, G. G. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5217-04.2005 · Cited by 306 · see citing works
Osten, P., Khatri, L., Perez, J. L., Köhr, G., Giese, G., Daly, C., Schulz, T. W., Wensky, A. K., Lee, L. M., & Ziff, E. B. (2000) · Neuron · doi:10.1016/s0896-6273(00)00039-8 · Cited by 295 · see citing works
Homeostatic Signaling and the Stabilization of Neural Function
Davis, G. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.044 · Cited by 271 · see citing works
Interaction between GRIP and Liprin-α/SYD2 Is Required for AMPA Receptor Targeting
Wyszynski, M. W., Kim, E., Dunah, A. W., Passafaro, M., Valtschanoff, J. G., Serra‐Pages, C., Streuli, M., Weinberg, R. J., & Sheng, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00640-2 · Cited by 255 · see citing works
Characterization of the Glutamate Receptor-Interacting Proteins GRIP1 and GRIP2
Dong, H., Zhang, P., Song, I., Petralia, R. S., Liao, D., & Huganir, R. L. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-16-06930.1999 · Cited by 245 · see citing works
Self-citationSynaptic scaling requires the GluR2 subunit of the AMPA receptor
Gainey, M. A., Hurvitz-Wolff, J. R., Lambo, M. E., & Turrigiano, G. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3753-08.2009 · Cited by 234 · see citing works
Seeburg, D. P., Feliú-Mójer, M. I., Gaiottino, J., Pak, D. T. S., & Sheng, M. (2008) · Neuron · doi:10.1016/j.neuron.2008.03.021 · Cited by 230 · see citing works
GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking
Hoogenraad, C. C., Milstein, A. D., Ethell, I. M., Henkemeyer, M. J., & Sheng, M. (2005) · Nature Neuroscience · doi:10.1038/nn1487 · Cited by 226 · see citing works
Activity-Dependent Regulation of Synaptic AMPA Receptor Composition and Abundance by β3 Integrins
Cingolani, L. A., Thalhammer, A., Yu, L. M. Y., Catalano, M., Ramos, T., Colicos, M. A., & Goda, Y. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.011 · Cited by 223 · see citing works
Association of the Kinesin Motor KIF1A with the Multimodular Protein Liprin-α
Shin, H., Wyszynski, M. W., Huh, K. H., Valtschanoff, J. G., Lee, J.-R., Ko, J., Streuli, M., Weinberg, R. J., Sheng, M., & Kim, E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211874200 · Cited by 207 · see citing works
Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-R trafficking
Thomas, G. M., Hayashi, T., Chen, C.-M., Chiu, S.-L., & Huganir, R. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.021 · Cited by 181 · see citing works
Self-citationDiering, G. H., Gustina, A. S., & Huganir, R. L. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.024 · Cited by 153 · see citing works
Self-citationTakamiya, K., Kostourou, V., Adams, S., Jadeja, S., Chalepakis, G., Scambler, P. J., Huganir, R. L., & Adams, R. H. (2004) · Nature Genetics · doi:10.1038/ng1292 · Cited by 147 · see citing works
Self-citationSteinmetz, C. C., & Turrigiano, G. G. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.2210-10.2010 · Cited by 146 · see citing works
PSD-95 and PSD-93 Play Critical But Distinct Roles in Synaptic Scaling Up and Down
Sun, Q., & Turrigiano, G. G. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5616-10.2011 · Cited by 135 · see citing works
Differential roles for NSF and GRIP/ABP in AMPA receptor cycling
Braithwaite, S. P., Xia, H., & Malenka, R. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102156099 · Cited by 131 · see citing works
deSouza, S., Fu, J., States, B. A., & Ziff, E. B. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03493.2002 · Cited by 123 · see citing works
Kelleher III, R. J., Geigenmüller, U., Hovhannisyan, H., Trautman, E., Pinard, R., Rathmell, B., Carpenter, R., & Margulies, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035003 · Cited by 116 · see citing works
Calcineurin mediates synaptic scaling via synaptic trafficking of Ca2+-permeable AMPA receptors
Kim, S., & Ziff, E. B. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001900 · Cited by 114 · see citing works
Triad3A Regulates Synaptic Strength by Ubiquitination of Arc
Mabb, A. M., Je, H. S., Wall, M. J., Robinson, C. G., Larsen, R. S., Yuan, Q., Corrêa, S. A. L., & Ehlers, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.016 · Cited by 113 · 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 and 2 regulate activity-dependent AMPA receptor recycling via exocyst complex interactions
Mao, L., Takamiya, K., Thomas, G., Lin, D.-T., & Huganir, R. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013494107 · Cited by 94 · see citing works
Self-citationMejı́as, R., Adamczyk, A. L., Anggono, V., Niranjan, T., Thomas, G. M., Sharma, K., Skinner, C. D., Schwartz, C. E., Stevenson, R. E., Fallin, M. D., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102233108 · Cited by 86 · see citing works
Self-citationScudder, S. L., Goo, M. S., Cartier, A. E., Molteni, A., Schwarz, L. A., Wright, R., & Patrick, G. N. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2452-14.2014 · Cited by 81 · see citing works
Takamiya, K., Mao, L., Huganir, R. L., & Linden, D. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0654-08.2008 · Cited by 72 · see citing works
Self-citationEpidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1
Bladt, F., Tafuri, A., Gelkop, S., Langille, L. B., & Pawson, T. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092130099 · Cited by 69 · see citing works
The GRIP1/14-3-3 Pathway Coordinates Cargo Trafficking and Dendrite Development
Geiger, J. C., Lipka, J., Segura, I., Hoyer, S. C., Schlager, M. A., Wulf, P. S., Weinges, S., Demmers, J., Hoogenraad, C. C., & Acker‐Palmer, A. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.01.018 · Cited by 29 · see citing works
Differential roles of GRIP1a and GRIP1b in AMPA receptor trafficking
Hanley, L. J., & Henley, J. M. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.09.003 · Cited by 27 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB (1998) Activity- dependent scaling of quantal amplitude in neocortical neurons. Nature 391(6670): 892-896.
- Fu AKY, et al. (2011) APC(Cdh1) mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity. Nat Neurosci 14(2):181-189.
- Hu JH, et al. (2010) Homeostatic scaling requires group I mGluR activation mediated by Homer1a. Neuron 68(6):1128-1142.
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Menon, S., Goldfarb, D., Ho, C. T., Cloer, E. W., Boyer, N. P., Hardie, C., Bock, A. J., Johnson, E. C., Anil, J., Major, M. B., et al. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e20-10-0622 · Cited by 46 · see citing works
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- Authors
- Tan, H. L., Queenan, B. N., & Huganir, R. L.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-07-27
- Volume
- 112
- Issue
- 32
- Pages
- 10026-10031
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4538612
- OpenAlex
- W1945016781
- Cited by
- 69
- References
- 46
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 3 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 5
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | 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 › Neural dynamics and brain function
- Keywords
- GRIP1, AMPA receptor trafficking, homeostatic plasticity, synaptic scaling, GluA2, PDZ domain, postsynaptic density, excitatory synapses
- MeSH terms
- Analysis of Variance, Animals, Carrier Proteins, Cell Membrane, Homeostasis, Models, Neurological, Nerve Tissue Proteins, Neurons, Subcellular Fractions, Synapses, Tetrodotoxin, Receptors, AMPA, Mice, Knockout, Protein Transport, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Rats
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