Abstract
Interaction with the multi-PDZ protein GRIP is required for the synaptic targeting of AMPA receptors, but the underlying mechanism is unknown. We show that GRIP binds to the liprin-alpha/SYD2 family of proteins that interact with LAR receptor protein tyrosine phosphatases (LAR-RPTPs) and that are implicated in presynaptic development. In neurons, liprin-alpha and LAR-RPTP are enriched at synapses and coimmunoprecipitate with GRIP and AMPA receptors. Dominant-negative constructs that interfere with the GRIP-liprin interaction disrupt the surface expression and dendritic clustering of AMPA receptors in cultured neurons. Thus, by mediating the targeting of liprin/GRIP-associated proteins, liprin-alpha is important for postsynaptic as well as presynaptic maturation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Brain / cytology
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Brain / metabolism
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COS Cells
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Carrier Proteins / metabolism*
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Cells, Cultured
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Embryo, Mammalian
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism
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Neurons / ultrastructure
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Phosphoproteins / metabolism*
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Protein Tyrosine Phosphatases*
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Rats
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Receptor-Like Protein Tyrosine Phosphatases, Class 2
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Receptors, AMPA / metabolism*
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Receptors, Cell Surface / metabolism
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Synapses / metabolism
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Synapses / ultrastructure
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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GRIP1 protein, human
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Grip1 protein, rat
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Phosphoproteins
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Ppfia4 protein, rat
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Receptors, AMPA
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Receptors, Cell Surface
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PTPRF protein, human
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Protein Tyrosine Phosphatases
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Ptprf protein, rat
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Receptor-Like Protein Tyrosine Phosphatases, Class 2