Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation
Open accessAbstract
The functional roles of protein tyrosine phosphatases (PTPs) in the developed CNS have been enigmatic. Here we show that striatal enriched tyrosine phosphatase (STEP) is a component of the N-methyl-D-aspartate receptor (NMDAR) complex. Functionally, exogenous STEP depressed NMDAR single-channel activity in excised membrane patches. STEP also depressed NMDAR-mediated synaptic currents whereas inhibiting endogenous STEP enhanced these currents. In hippocampal slices, administering STEP into CA1 neurons did not affect basal glutamatergic transmission evoked by Schaffer collateral stimulation but prevented tetanus-induced long-term potentiation (LTP). Conversely, inhibiting STEP in CA1 neurons enhanced transmission and occluded LTP induction through an NMDAR-, Src-, and Ca(2+)-dependent mechanism. Thus, STEP acts as a tonic brake on synaptic transmission by opposing Src-dependent upregulation of NMDARs.
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Aβ-mediated activation of STEP leads to excessive internalization of NMDARs.
“Thus, Aβ-mediated activation of STEP leads to excessive internalization of NMDARs [28, 35].”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [35]
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- Authors
- Pelkey, K. A., Askalan, R., Paul, S., Kalia, L. V., Nguyen, T.-H., Pitcher, G. M., Salter, M. W., & Lombroso, P. J.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Yale University (US)
- Corresponding author
- Salter, Michael W.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 34
- Issue
- 1
- Pages
- 127-138
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2079862834
- Cited by
- 208
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 2 · 2021: 9 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 8 · 2014: 10 · 2013: 13 · 2012: 18
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4156 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- STEP, protein tyrosine phosphatase, NMDA receptor, long-term potentiation, synaptic transmission, Src kinase, calcium signaling, tetanic stimulation, CA1 neurons, hippocampus, glutamatergic synapses
- MeSH terms
- Animals, Cells, Cultured, Corpus Striatum, Embryo, Mammalian, Hippocampus, Male, Synaptic Transmission, Receptors, N-Methyl-D-Aspartate, Protein Tyrosine Phosphatases, Rats, Wistar, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Rats, Protein Tyrosine Phosphatases, Non-Receptor, In Vitro Techniques
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