LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses

Anthone W Dunah; Emily Hueske; Michael Wyszynski; Casper C Hoogenraad; Jacek Jaworski; Daniel T Pak; Alyson Simonetta; Guosong Liu; Morgan Sheng

doi:10.1038/nn1416

LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses

Anthone W Dunah, Emily Hueske, Michael Wyszynski, Casper C Hoogenraad, Jacek Jaworski, Daniel T Pak, Alyson Simonetta, Guosong Liu, Morgan Sheng

Sub Cell Biology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (LAR-RPTP) bind to liprin-alpha (SYD2) and are implicated in axon guidance. We report that LAR-RPTP is concentrated in mature synapses in cultured rat hippocampal neurons, and is important for the development and maintenance of excitatory synapses in hippocampal neurons. RNA interference (RNAi) knockdown of LAR or dominant-negative disruption of LAR function results in loss of excitatory synapses and dendritic spines, reduction of surface AMPA receptors, impairment of dendritic targeting of the cadherin-beta-catenin complex, and reduction in the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). Cadherin, beta-catenin and GluR2/3 are tyrosine phosphoproteins that coimmunoprecipitate with liprin-alpha and GRIP from rat brain extracts. We propose that the cadherin-beta-catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin-alpha to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP.

Original language	English
Pages (from-to)	458-67
Number of pages	10
Journal	Nature Neuroscience
Volume	8
Issue number	4
DOIs	https://doi.org/10.1038/nn1416
Publication status	Published - Apr 2005

Keywords

Adaptor Proteins, Signal Transducing
Animals
Animals, Newborn
Blotting, Western
Brain
COS Cells
Cells, Cultured
Cercopithecus aethiops
Cytoskeletal Proteins
Dendrites
Diagnostic Imaging
Enzyme Inhibitors
Excitatory Postsynaptic Potentials
Gene Expression Regulation, Developmental
Genistein
Green Fluorescent Proteins
Hippocampus
Humans
Immunohistochemistry
Immunoprecipitation
Membrane Potentials
Molecular Sequence Data
Mutagenesis
Nerve Tissue Proteins
Neurons
Patch-Clamp Techniques
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Phosphoproteins
Phosphoric Monoester Hydrolases
Phosphorylation
Protein Tyrosine Phosphatases
Proto-Oncogene Proteins c-myc
RNA, Antisense
RNA, Small Interfering
Rats
Receptor-Like Protein Tyrosine Phosphatases, Class 2
Receptors, AMPA
Receptors, Cell Surface
Receptors, N-Methyl-D-Aspartate
Synapses
Time Factors
Trans-Activators
Transfection
Tyrosine
Vanadates
beta Catenin

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10.1038/nn1416

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title = "LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses",

abstract = "Leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (LAR-RPTP) bind to liprin-alpha (SYD2) and are implicated in axon guidance. We report that LAR-RPTP is concentrated in mature synapses in cultured rat hippocampal neurons, and is important for the development and maintenance of excitatory synapses in hippocampal neurons. RNA interference (RNAi) knockdown of LAR or dominant-negative disruption of LAR function results in loss of excitatory synapses and dendritic spines, reduction of surface AMPA receptors, impairment of dendritic targeting of the cadherin-beta-catenin complex, and reduction in the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). Cadherin, beta-catenin and GluR2/3 are tyrosine phosphoproteins that coimmunoprecipitate with liprin-alpha and GRIP from rat brain extracts. We propose that the cadherin-beta-catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin-alpha to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP.",

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author = "Dunah, {Anthone W} and Emily Hueske and Michael Wyszynski and Hoogenraad, {Casper C} and Jacek Jaworski and Pak, {Daniel T} and Alyson Simonetta and Guosong Liu and Morgan Sheng",

year = "2005",

month = apr,

doi = "10.1038/nn1416",

language = "English",

volume = "8",

pages = "458--67",

journal = "Nature Neuroscience",

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T1 - LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses

AU - Dunah, Anthone W

AU - Hueske, Emily

AU - Wyszynski, Michael

AU - Hoogenraad, Casper C

AU - Jaworski, Jacek

AU - Pak, Daniel T

AU - Simonetta, Alyson

AU - Liu, Guosong

AU - Sheng, Morgan

PY - 2005/4

Y1 - 2005/4

N2 - Leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (LAR-RPTP) bind to liprin-alpha (SYD2) and are implicated in axon guidance. We report that LAR-RPTP is concentrated in mature synapses in cultured rat hippocampal neurons, and is important for the development and maintenance of excitatory synapses in hippocampal neurons. RNA interference (RNAi) knockdown of LAR or dominant-negative disruption of LAR function results in loss of excitatory synapses and dendritic spines, reduction of surface AMPA receptors, impairment of dendritic targeting of the cadherin-beta-catenin complex, and reduction in the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). Cadherin, beta-catenin and GluR2/3 are tyrosine phosphoproteins that coimmunoprecipitate with liprin-alpha and GRIP from rat brain extracts. We propose that the cadherin-beta-catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin-alpha to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP.

AB - Leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (LAR-RPTP) bind to liprin-alpha (SYD2) and are implicated in axon guidance. We report that LAR-RPTP is concentrated in mature synapses in cultured rat hippocampal neurons, and is important for the development and maintenance of excitatory synapses in hippocampal neurons. RNA interference (RNAi) knockdown of LAR or dominant-negative disruption of LAR function results in loss of excitatory synapses and dendritic spines, reduction of surface AMPA receptors, impairment of dendritic targeting of the cadherin-beta-catenin complex, and reduction in the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). Cadherin, beta-catenin and GluR2/3 are tyrosine phosphoproteins that coimmunoprecipitate with liprin-alpha and GRIP from rat brain extracts. We propose that the cadherin-beta-catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin-alpha to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP.

KW - Adaptor Proteins, Signal Transducing

KW - Animals

KW - Animals, Newborn

KW - Blotting, Western

KW - Brain

KW - COS Cells

KW - Cells, Cultured

KW - Cercopithecus aethiops

KW - Cytoskeletal Proteins

KW - Dendrites

KW - Diagnostic Imaging

KW - Enzyme Inhibitors

KW - Excitatory Postsynaptic Potentials

KW - Gene Expression Regulation, Developmental

KW - Genistein

KW - Green Fluorescent Proteins

KW - Hippocampus

KW - Humans

KW - Immunohistochemistry

KW - Immunoprecipitation

KW - Membrane Potentials

KW - Molecular Sequence Data

KW - Mutagenesis

KW - Nerve Tissue Proteins

KW - Neurons

KW - Patch-Clamp Techniques

KW - Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase

KW - Phosphoproteins

KW - Phosphoric Monoester Hydrolases

KW - Phosphorylation

KW - Protein Tyrosine Phosphatases

KW - Proto-Oncogene Proteins c-myc

KW - RNA, Antisense

KW - RNA, Small Interfering

KW - Rats

KW - Receptor-Like Protein Tyrosine Phosphatases, Class 2

KW - Receptors, AMPA

KW - Receptors, Cell Surface

KW - Receptors, N-Methyl-D-Aspartate

KW - Synapses

KW - Time Factors

KW - Trans-Activators

KW - Transfection

KW - Tyrosine

KW - Vanadates

KW - beta Catenin

U2 - 10.1038/nn1416

DO - 10.1038/nn1416

M3 - Article

C2 - 15750591

SN - 1097-6256

VL - 8

SP - 458

EP - 467

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 4

ER -

LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses

Abstract

Keywords

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