Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation.
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.
Pelkey
Kenneth A
KA
Department of Physiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Askalan
Rand
R
Paul
Surojit
S
Kalia
Lorraine V
LV
Nguyen
Tri Hung
TH
Pitcher
Graham M
GM
Salter
Michael W
MW
Lombroso
Paul J
PJ
D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C489931:Ptpn5 protein, rat