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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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

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spelling	todo:paper_19326203_v7_n7_p_Fuentes2023-10-03T16:35:23Z Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning Fuentes, F. Zimmer, D. Atienza, M. Schottenfeld, J. Penkala, I. Bale, T. Bence, K.K. Arregui, C.O. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v7_n7_p_Fuentes
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Fuentes, F. Zimmer, D. Atienza, M. Schottenfeld, J. Penkala, I. Bale, T. Bence, K.K. Arregui, C.O. Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning
topic_facet	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
description	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.
format	JOUR
author	Fuentes, F. Zimmer, D. Atienza, M. Schottenfeld, J. Penkala, I. Bale, T. Bence, K.K. Arregui, C.O.
author_facet	Fuentes, F. Zimmer, D. Atienza, M. Schottenfeld, J. Penkala, I. Bale, T. Bence, K.K. Arregui, C.O.
author_sort	Fuentes, F.
title	Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning
title_short	Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning
title_full	Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning
title_fullStr	Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning
title_full_unstemmed	Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning
title_sort	protein tyrosine phosphatase ptp1b is involved in hippocampal synapse formation and learning
url	http://hdl.handle.net/20.500.12110/paper_19326203_v7_n7_p_Fuentes
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_version_	1807318980512186368

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

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