The 4.1 protein coracle mediates subunit-selective anchoring of Drosophila glutamate receptors to the postsynaptic actin cytoskeleton.
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.
Chen
Kaiyun
K
Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Merino
Carlos
C
Sigrist
Stephan J
SJ
Featherstone
David E
DE
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
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