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

Kenneth A Pelkey; Rand Askalan; Surojit Paul; Lorraine V Kalia; Tri Hung Nguyen; Graham M Pitcher; Michael W Salter; Paul J Lombroso

doi:10.1016/s0896-6273(02)00633-5

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

Neuron. 2002 Mar 28;34(1):127-38. doi: 10.1016/s0896-6273(02)00633-5.

Authors

Kenneth A Pelkey¹, Rand Askalan, Surojit Paul, Lorraine V Kalia, Tri Hung Nguyen, Graham M Pitcher, Michael W Salter, Paul J Lombroso

Affiliation

¹ Department of Physiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.

PMID: 11931747
DOI: 10.1016/s0896-6273(02)00633-5

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Cells, Cultured
Corpus Striatum / cytology
Corpus Striatum / physiology
Embryo, Mammalian
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / physiology
Hippocampus / cytology
Hippocampus / physiology
In Vitro Techniques
Long-Term Potentiation / drug effects
Long-Term Potentiation / physiology*
Male
Protein Tyrosine Phosphatases / antagonists & inhibitors
Protein Tyrosine Phosphatases / pharmacology
Protein Tyrosine Phosphatases / physiology*
Protein Tyrosine Phosphatases, Non-Receptor
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate / physiology
Synaptic Transmission / drug effects
Synaptic Transmission / physiology

Substances

Receptors, N-Methyl-D-Aspartate
Protein Tyrosine Phosphatases
Protein Tyrosine Phosphatases, Non-Receptor
Ptpn5 protein, rat