LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses.
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.
Dunah
Anthone W
AW
The Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Cambridge, Massachusetts 02139, USA.
Hueske
Emily
E
Wyszynski
Michael
M
Hoogenraad
Casper C
CC
Jaworski
Jacek
J
Pak
Daniel T
DT
Simonetta
Alyson
A
Liu
Guosong
G
Sheng
Morgan
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008564:Membrane Potentials / Q000235:genetics / Q000528:radiation effects; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016372:RNA, Antisense / Q000494:pharmacology; D034741:RNA, Small Interfering; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D018091:Receptors, AMPA / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C498440:BSN protein, human; C113688:Bsn protein, rat; C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; C094398:PPFIA1 protein, human; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D015534:Trans-Activators; D051176:beta Catenin; C076715:pervanadate; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D014638:Vanadates; D014443:Tyrosine; D019833:Genistein; D010744:Phosphoric Monoester Hydrolases; C516772:PTPRF protein, human; D017027:Protein Tyrosine Phosphatases; C516774:Ptprf protein, rat; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase