Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning

ER-bound PTP1B is expressed in hippocampal neurons, and accumulates among neurite contacts. PTP1B dephosphorylates ß-catenin in N-cadherin complexes ensuring cell-cell adhesion. Here we show that endogenous PTP1B, as well as expressed GFP-PTP1B, are present in dendritic spines of hippocampal neurons...

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Detalles Bibliográficos
Autores principales: Fuentes, F., Zimmer, D., Atienza, M., Schottenfeld, J., Penkala, I., Bale, T., Bence, K.K., Arregui, C.O.
Formato: JOUR
Materias:
beta catenin
nerve cell adhesion molecule
postsynaptic density protein 95
protein tyrosine phosphatase 1B
synapsin I
tyrosine
animal cell
animal experiment
animal tissue
article
brain cortex
cell elongation
cell structure
controlled study
dendritic spine
embryo
enzyme activity
enzyme regulation
filopodium
hippocampus
learning
memory
mouse
nerve cell
nerve cell plasticity
newborn
nonhuman
phenotype
protein analysis
protein deficiency
protein expression
protein function
protein phosphorylation
rat
recall
Animals
beta Catenin
Cadherins
Dendritic Spines
Female
Gene Deletion
Hippocampus
Learning
Memory
Mice
Neuronal Plasticity
Phosphorylation
Pregnancy
Protein Transport
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Rats
Synapses
Tyrosine
Basidiomycota
Mus
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19326203_v7_n7_p_Fuentes
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:ER-bound PTP1B is expressed in hippocampal neurons, and accumulates among neurite contacts. PTP1B dephosphorylates ß-catenin in N-cadherin complexes ensuring cell-cell adhesion. Here we show that endogenous PTP1B, as well as expressed GFP-PTP1B, are present in dendritic spines of hippocampal neurons in culture. GFP-PTP1B overexpression does not affect filopodial density or length. In contrast, impairment of PTP1B function or genetic PTP1B-deficiency leads to increased filopodia-like dendritic spines and a reduction in mushroom-like spines, while spine density is unaffected. These morphological alterations are accompanied by a disorganization of pre- and post-synapses, as judged by decreased clustering of synapsin-1 and PSD-95, and suggest a dynamic synaptic phenotype. Notably, levels of ß-catenin-Tyr-654 phosphorylation increased ~5-fold in the hippocampus of adult PTP1B-/- (KO) mice compared to wild type (WT) mice and this was accompanied by a reduction in the amount of ß-catenin associated with N-cadherin. To determine whether PTP1B-deficiency alters learning and memory, we generated mice lacking PTP1B in the hippocampus and cortex (PTP1Bfl/fl-Emx1-Cre). PTP1Bfl/fl-Emx1-Cre mice displayed improved performance in the Barnes maze (decreased time to find and enter target hole), utilized a more efficient strategy (cued), and had better recall compared to WT controls. Our results implicate PTP1B in structural plasticity within the hippocampus, likely through modulation of N-cadherin function by ensuring dephosphorylation of ß-catenin on Tyr-654. Disruption of hippocampal PTP1B function or expression leads to elongation of dendritic filopodia and improved learning and memory, demonstrating an exciting novel role for this phosphatase. © 2012 Fuentes et al.

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