An essential role for inhibitor-2 regulation of protein phosphatase-1 in synaptic scaling
Open accessAbstract
Protein phosphatase-1 (PP1) activity is important for many calcium-dependent neuronal functions including Hebbian synaptic plasticity and learning and memory. PP1 activity is necessary for the induction of long-term depression, whereas downregulation of PP1 activity is required for the normal induction of long-term potentiation. However, how PP1 is activated is not clear. Moreover, it is not known whether PP1 plays a role in homeostatic synaptic scaling, another form of synaptic plasticity which functions to reset the neuronal firing rate in response to chronic neuronal activity perturbations. In this study, we found that PP1 inhibitor-2 (I-2) is phosphorylated at serine 43 (S43) in rat and mouse cortical neurons in response to bicuculine application. Expression of I-2 phosphorylation-blocking mutant I-2 (S43A) blocked the dephosphorylation of GluA2 at serine 880, AMPA receptor trafficking, and synaptic downscaling induced by bicuculline application. Our data suggest that the phosphorylation of I-2 at S43 appears to be mediated by L-type calcium channels and calcium/calmodulin-dependent myosin light-chain kinase. Our work thus reveals a novel calcium-induced PP1 activation pathway critical for homeostatic synaptic plasticity.
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Dephosphorylation of GluA2 S880 during scaling-down is mediated by activation of phosphatase PP1 through its regulatory protein inhibitor 2 (I-2), while dephosphorylation of GluA2 Y876 requires an upregulation of STEP61.
“Dephosphorylation of GluA2 S880 during scaling-down is mediated by activation of phosphatase PP1, through its regulatory protein inhibitor 2 (I-2) (Siddoway et al., 2013), while dephosphorylation of GluA2 Y876 requires an upregulation of STEP61 (Jang et al., 2015).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Siddoway et al., 2013
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Cited by
Sorted by citations
The 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
- Authors
- Siddoway, B. A., Altimimi, H. F., Hou, H., Petralia, R. S., Xu, B., Stellwagen, D., & Xia, H.
- Affiliations
- Louisiana State University (US)
- McGill University (CA)
- National Institutes of Health (US)
- Southern Research Institute (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-07-03
- Volume
- 33
- Issue
- 27
- Pages
- 11206-11211
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3718377
- OpenAlex
- W2094995262
- Cited by
- 32
- References
- 3
- Citations by year
- 2026: 1 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 1
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0824393)
- Heart and Stroke Foundation of Canada
- National Alliance for Research on Schizophrenia and Depression (2006YI)
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute on Deafness and Other Communication Disorders
- National Institute of Neurological Disorders and Stroke (R01NS060879)
- National Institute of Environmental Health Sciences (R01ES016354)
- Division of Integrative Organismal Systems
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- protein phosphatase 1, homeostatic synaptic scaling, synaptic plasticity, AMPA receptor trafficking, bicuculline, L-type calcium channels, cortical neurons, long-term depression, long-term potentiation
- MeSH terms
- Protein Phosphatase Inhibitory Proteins, Animals, Animals, Newborn, Cells, Cultured, Homeostasis, Synaptic Transmission, Proteins, Synapses, Rats, Sprague-Dawley, Mice, Knockout, Calcium Channels, L-Type, Mice, Rats, Protein Phosphatase 1
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