Abstract
The PDZ domain-containing proteins, such as PSD-95 and GRIP, have been suggested to be involved in the targeting of glutamate receptors, a process that plays a critical role in the efficiency of synaptic transmission and plasticity. To address the molecular mechanisms underlying AMPA receptor synaptic localization, we have identified several GRIP-associated proteins (GRASPs) that bind to distinct PDZ domains within GRIP. GRASP-1 is a neuronal rasGEF associated with GRIP and AMPA receptors in vivo. Overexpression of GRASP-1 in cultured neurons specifically reduced the synaptic targeting of AMPA receptors. In addition, the subcellular distribution of both AMPA receptors and GRASP-1 was rapidly regulated by the activation of NMDA receptors. These results suggest that GRASP-1 may regulate neuronal ras signaling and contribute to the regulation of AMPA receptor distribution by NMDA receptor activity.
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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Amino Acid Sequence / genetics
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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Caspase 3
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Caspases / metabolism
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Cloning, Molecular
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Intracellular Signaling Peptides and Proteins
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Male
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Membrane Proteins
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Molecular Sequence Data
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism*
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Protein Isoforms / metabolism*
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / metabolism*
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Receptors, N-Methyl-D-Aspartate / physiology
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Substrate Specificity
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Synapses / metabolism
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Tissue Distribution
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ras Guanine Nucleotide Exchange Factors / genetics
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ras Guanine Nucleotide Exchange Factors / metabolism*
Substances
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Carrier Proteins
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GRIPAP1 protein, human
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Grip1 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Protein Isoforms
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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ras Guanine Nucleotide Exchange Factors
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tamalin protein, human
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CASP3 protein, human
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Casp3 protein, rat
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Caspase 3
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Caspases
Associated data
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GENBANK/AF040944
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GENBANK/AF274057