title: Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses.
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.
authors.affiliation: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Siqiong June
authors.initials: SJ
authors.lastname: Liu
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Cull-Candy
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D010446:Peptide Fragments; D021122:Protein Subunits; D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium