Abstract
At many excitatory central synapses, activity produces a lasting change in the synaptic response by modifying postsynaptic AMPA receptors (AMPARs). Although much is known about proteins involved in the trafficking of Ca2+-impermeable (GluR2-containing) AMPARs, little is known about protein partners that regulate subunit trafficking and plasticity of Ca2+-permeable (GluR2-lacking) AMPARs. At cerebellar parallel fiber-stellate cell synapses, activity triggers a novel type of plasticity: Ca2+ influx through GluR2-lacking synaptic AMPARs drives incorporation of GluR2-containing AMPARs, generating rapid, lasting changes in excitatory postsynaptic current properties. Here we examine how glutamate receptor interacting protein (GRIP, also known as AMPAR binding protein or ABP) and protein interacting with C-kinase-1 (PICK) regulate subunit trafficking and plasticity. We find that repetitive synaptic activity triggers loss of synaptic GluR2-lacking AMPARs by selectively disrupting their interaction with GRIP and that PICK drives activity-dependent delivery of GluR2-containing receptors. This dynamic regulation of AMPARs provides a feedback mechanism for controlling Ca2+ permeability of synaptic receptors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Calcium / metabolism
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Calcium Channels / drug effects
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Calcium Channels / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Carrier Proteins / drug effects
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Carrier Proteins / metabolism*
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Cell Membrane Permeability / drug effects
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Cell Membrane Permeability / physiology
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Cerebellar Cortex / drug effects
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Cerebellar Cortex / metabolism*
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Cytoskeletal Proteins
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / metabolism*
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Neuronal Plasticity / physiology
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Nuclear Proteins / drug effects
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Nuclear Proteins / metabolism*
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Organ Culture Techniques
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Patch-Clamp Techniques
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Peptide Fragments / pharmacology
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Protein Subunits / drug effects
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Protein Subunits / metabolism
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Protein Transport / physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism*
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Sodium Channel Blockers / pharmacology
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Calcium Channels
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Carrier Proteins
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Cytoskeletal Proteins
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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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Nuclear Proteins
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PICK1 protein, rat
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Peptide Fragments
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Protein Subunits
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Receptors, AMPA
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Sodium Channel Blockers
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glutamate receptor ionotropic, AMPA 2
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Calcium