PMID- 21501258
OWN - NLM
STAT- MEDLINE
DCOM- 20111024
LR  - 20211020
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 33
IP  - 12
DP  - 2011 Jun
TI  - Striatal-enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced 
      hippocampal memory.
PG  - 2288-98
LID - 10.1111/j.1460-9568.2011.07687.x [doi]
AB  - Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific 
      phosphatase that opposes synaptic strengthening by the regulation of key synaptic 
      signaling proteins. Previous studies suggest a possible role for STEP in learning 
      and memory. To demonstrate the functional importance of STEP in learning and 
      memory, we generated STEP knockout (KO) mice and examined the effect of deletion 
      of STEP on behavioral performance, as well as the phosphorylation and expression 
      of its substrates. Here we report that loss of STEP leads to significantly 
      enhanced performance in hippocampal-dependent learning and memory tasks. In 
      addition, STEP KO mice displayed greater dominance behavior, although they were 
      normal in their motivation, motor coordination, visual acuity and social 
      interactions. STEP KO mice displayed enhanced tyrosine phosphorylation of 
      extracellular-signal regulated kinase 1/2 (ERK1/2), the NR2B subunit of the 
      N-methyl-D-aspartate receptor (NMDAR) and proline-rich tyrosine kinase (Pyk2), as 
      well as an increased phosphorylation of ERK1/2 substrates. Concomitant with the 
      increased phosphorylation of NR2B, synaptosomal expression of NR1/NR2B NMDARs was 
      increased in STEP KO mice, as was the GluR1/GluR2 containing 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs), 
      providing a potential molecular mechanism for the improved cognitive performance. 
      The data support a role for STEP in the regulation of synaptic strengthening. The 
      absence of STEP improves cognitive performance, and may do so by the regulation 
      of downstream effectors necessary for synaptic transmission.
CI  - (c) 2011 The Authors. European Journal of Neuroscience (c) 2011 Federation of 
      European Neuroscience Societies and Blackwell Publishing Ltd.
FAU - Venkitaramani, Deepa V
AU  - Venkitaramani DV
AD  - Child Study Center, Yale University School of Medicine, New Haven, CT, USA. 
      dvenkita@illinois.edu
FAU - Moura, Paula J
AU  - Moura PJ
FAU - Picciotto, Marina R
AU  - Picciotto MR
FAU - Lombroso, Paul J
AU  - Lombroso PJ
LA  - eng
GR  - K02 MH001527-10/MH/NIMH NIH HHS/United States
GR  - K02 MH001527/MH/NIMH NIH HHS/United States
GR  - R01 MH052711-18/MH/NIMH NIH HHS/United States
GR  - R37 DA014241/DA/NIDA NIH HHS/United States
GR  - R01 DA014241/DA/NIDA NIH HHS/United States
GR  - MH52711/MH/NIMH NIH HHS/United States
GR  - DA14241/DA/NIDA NIH HHS/United States
GR  - R01 DA014241-08/DA/NIDA NIH HHS/United States
GR  - R01 MH052711/MH/NIMH NIH HHS/United States
GR  - MH01527/MH/NIMH NIH HHS/United States
GR  - R01 MH091037/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110419
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
RN  - EC 3.1.3.48 (Ptpn5 protein, mouse)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*physiology
MH  - Focal Adhesion Kinase 2/metabolism
MH  - Hippocampus/metabolism/*physiology
MH  - Memory/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phosphorylation/genetics
MH  - Protein Tyrosine Phosphatases, Non-Receptor/genetics/*physiology
MH  - Receptors, AMPA/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Synaptic Transmission/genetics/*physiology
PMC - PMC3118976
MID - NIHMS283923
EDAT- 2011/04/20 06:00
MHDA- 2011/10/25 06:00
PMCR- 2012/06/01
CRDT- 2011/04/20 06:00
PHST- 2011/04/20 06:00 [entrez]
PHST- 2011/04/20 06:00 [pubmed]
PHST- 2011/10/25 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - 10.1111/j.1460-9568.2011.07687.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2011 Jun;33(12):2288-98. doi: 10.1111/j.1460-9568.2011.07687.x. 
      Epub 2011 Apr 19.