title: The 4.1 protein coracle mediates subunit-selective anchoring of Drosophila glutamate receptors to the postsynaptic actin cytoskeleton.
abstract: Glutamatergic Drosophila neuromuscular junctions contain two spatially, biophysically, and pharmacologically distinct subtypes of postsynaptic glutamate receptor (GluR). These receptor subtypes appear to be molecularly identical except that A receptors contain the subunit GluRIIA (but not GluRIIB), and B receptors contain the subunit GluRIIB (but not GluRIIA). A- and B-type receptors are coexpressed in the same cells, in which they form homotypic clusters. During development, A- and B-type receptors can be differentially regulated. The mechanisms that allow differential segregation and regulation of A- and B-type receptors are unknown. Presumably, A- and B-type receptors are differentially anchored to the membrane cytoskeleton, but essentially nothing is known about how Drosophila glutamate receptors are localized or anchored. We identified coracle, a homolog of mammalian brain 4.1 proteins, in yeast two-hybrid and genetic screens for proteins that interact with and localize Drosophila glutamate receptors. Coracle interacts with the C terminus of GluRIIA but not GluRIIB. To test whether coracle is required for glutamate receptor localization, we immunocytochemically and electrophysiologically examined receptors in coracle mutants. In coracle mutants, synaptic A-type receptors are lost, but there is no detectable change in B-type receptor function or localization. Pharmacological disruption of postsynaptic actin phenocopies the coracle mutants, suggesting that A-type receptors are anchored to the actin cytoskeleton via coracle, whereas B-type receptors are anchored at the synapse by another (yet unknown) mechanism.
authors: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors: Kaiyun
authors: K
authors: Chen
authors: Carlos
authors: C
authors: Merino
authors: Stephan J
authors: SJ
authors: Sigrist
authors: David E
authors: DE
authors: Featherstone
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D007814:Larva; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D009469:Neuromuscular Junction / Q000196:embryology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D020798:Two-Hybrid System Techniques
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D029721:Drosophila Proteins; D008565:Membrane Proteins; D017470:Receptors, Glutamate; D013844:Thiazoles; D053778:Thiazolidines; C442474:cora protein, Drosophila; C037067:latrunculin A