title: Critical postsynaptic density 95/disc large/zonula occludens-1 interactions by glutamate receptor 1 (GluR1) and GluR2 required at different subcellular sites.
abstract: Interactions between AMPA receptor subunits and proteins containing postsynaptic density 95/disc large/zonula occludens-1 (PDZ) domains have been shown to play critical roles in the proper trafficking of receptors to excitatory synapses. Synaptic accumulation of AMPA receptors containing the glutamate receptor 1 (GluR1) subunit can be driven by calcium/calmodulin-dependent protein kinase II activity or long-term potentiation and requires an interaction between GluR1 and a type I PDZ domain-containing protein. Synaptic incorporation of AMPA receptors with only GluR2 occurs continuously, and this requires an interaction between GluR2 and a type II PDZ domain-containing protein. We used dual-channel, two-photon laser scanning microscopy to provide high-resolution visualization and quantification of green fluorescent protein-tagged AMPA receptors in different subcellular compartments. We showed that mutations on GluR1 or GluR2 AMPA subunit that perturb interactions with PDZ domain proteins lead to the accumulation of these receptors at different subcellular sites. GluR1 mutants accumulate in the dendrite, whereas GluR2 mutants accumulate in dendritic spines. This suggests that the critical PDZ domain interactions are required for entry into spines for GluR1 and for entry into synapses for GluR2.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Piccini
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D046508:Culture Techniques; D003712:Dendrites / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D018091:Receptors, AMPA / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000737:chemistry* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D018091:Receptors, AMPA; D062826:Zonula Occludens-1 Protein; C569044:Tjp1 protein, rat; C033652:postsynaptic density proteins; C104722:glutamate receptor ionotropic, AMPA 2