NF-kappaB, IkappaB, and IRAK control glutamate receptor density at the Drosophila NMJ.
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.
Heckscher
Elizabeth S
ES
Department of Biochemistry and Biophysics, Programs in Neuroscience and Cell Biology, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158-2822, USA.
Fetter
Richard D
RD
Marek
Kurt W
KW
Albin
Stephanie D
SD
Davis
Graeme W
GW
D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila; D004594:Electrophysiology; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000502:physiology*; D008566:Membranes / Q000378:metabolism; D008854:Microscopy, Electron; D009132:Muscles / Q000294:innervation / Q000502:physiology; D009154:Mutation / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000235:genetics / Q000502:physiology
D020672:I-kappa B Proteins; D016328:NF-kappa B; D017470:Receptors, Glutamate; D053592:Interleukin-1 Receptor-Associated Kinases