Nature Neuroscience
8, 458 - 467 (2005)
Published online: 6 March 2005; | doi:10.1038/nn1416
LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapsesAnthone W Dunah1, 3, Emily Hueske1, Michael Wyszynski1, 3, Casper C Hoogenraad1, Jacek Jaworski1, 2, Daniel T Pak1, 3, Alyson Simonetta1, 2, Guosong Liu1
& Morgan Sheng1, 21
The Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Cambridge, Massachusetts 02139, USA. 2
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. 3
Present addresses: Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School and Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA (A.W.D.); Amgen, Thousand Oaks, California 91320, USA (M.W.); Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA (D.T.P).
Correspondence should be addressed to Morgan Sheng msheng@mit.eduLeukocyte common antigen−related (LAR) family receptor protein tyrosine phosphatases (LAR-RPTP) bind to liprin- (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− -catenin complex, and reduction in the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). Cadherin, -catenin and GluR2/3 are tyrosine phosphoproteins that coimmunoprecipitate with liprin- and GRIP from rat brain extracts. We propose that the cadherin--catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin- to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP.
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