Cited by 208Neuroscience and Neuropharmacology ResearchProtein Tyrosine PhosphatasesTreatment of Major Depression

Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation

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Pelkey, Kenneth A., Askalan, Rand, Paul, Surojit, Kalia, Lorraine V., Nguyen, Tri-Hung, Pitcher, Graham M., Salter, Michael W., Lombroso, Paul J.·2002·Neuron

Abstract

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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Crossref · 10.1016/s0896-6273(02)00633-5

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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.
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
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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