RRC ID 11134
Author Heckscher ES, Fetter RD, Marek KW, Albin SD, Davis GW.
Title NF-kappaB, IkappaB, and IRAK control glutamate receptor density at the Drosophila NMJ.
Journal Neuron
Abstract NF-kappaB signaling has been implicated in neurodegenerative disease, epilepsy, and neuronal plasticity. However, the cellular and molecular activity of NF-kappaB signaling within the nervous system remains to be clearly defined. Here, we show that the NF-kappaB and IkappaB homologs Dorsal and Cactus surround postsynaptic glutamate receptor (GluR) clusters at the Drosophila NMJ. We then show that mutations in dorsal, cactus, and IRAK/pelle kinase specifically impair GluR levels, assayed immunohistochemically and electrophysiologically, without affecting NMJ growth, the size of the postsynaptic density, or homeostatic plasticity. Additional genetic experiments support the conclusion that cactus functions in concert with, rather than in opposition to, dorsal and pelle in this process. Finally, we provide evidence that Dorsal and Cactus act posttranscriptionally, outside the nucleus, to control GluR density. Based upon our data we speculate that Dorsal, Cactus, and Pelle could function together, locally at the postsynaptic density, to specify GluR levels.
Volume 55(6)
Pages 859-73
Published 2007-9-20
DOI 10.1016/j.neuron.2007.08.005
PII S0896-6273(07)00616-2
PMID 17880891
PMC PMC2701504
MeSH Alleles Animals Blotting, Western Cytoplasm / metabolism Drosophila Electrophysiology I-kappa B Proteins / genetics I-kappa B Proteins / physiology* Image Processing, Computer-Assisted Immunohistochemistry Interleukin-1 Receptor-Associated Kinases / genetics Interleukin-1 Receptor-Associated Kinases / physiology* Membranes / metabolism Microscopy, Electron Muscles / innervation Muscles / physiology Mutation / physiology NF-kappa B / genetics NF-kappa B / physiology* Neuromuscular Junction / metabolism* Protein Processing, Post-Translational / genetics Protein Processing, Post-Translational / physiology Receptors, Glutamate / genetics Receptors, Glutamate / metabolism* Reverse Transcriptase Polymerase Chain Reaction Synapses / genetics Synapses / physiology
IF 14.415
Times Cited 51
WOS Category NEUROSCIENCES
Resource
Drosophila 5974R-1 5974R-3