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Cited by 72Neuroscience and Neuropharmacology ResearchNF-κB Signaling PathwaysNeurobiology and Insect Physiology Research

NF-κB, IκB, and IRAK Control Glutamate Receptor Density at the Drosophila NMJ

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Heckscher, Elizabeth S., Fetter, Richard D., Marek, Kurt W., Albin, Stephanie D., Davis, Graeme W.·2007·Neuron
DOI 10.1016/j.neuron.2007.08.005PMC PMC2701504
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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.

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  1. [1]1. Albin, S.D. ∙ Davis, G.W. Coordinating structural and functional synapse development: postsynaptic p21-activated kinase independently specifies glutamate receptor abundance and postsynaptic morphology J. Neurosci. 2004; 24:6871-6879 Crossref Scopus (57) PubMed Google Scholar
  2. [2]2. Ashmore, L.J. ∙ Sathyanarayanan, S. ∙ Silvestre, D.W. ... Novel insights into the regulation of the timeless protein J. Neurosci. 2003; 23:7810-7819 Crossref PubMed Google Scholar
  3. [3]3. Baghdiguian, S. ∙ Martin, M. ∙ Richard, I. ... Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IkappaB alpha/NF-kappaB pathway in limb-girdle muscular dystrophy type 2A Nat. Med. 1999; 5:503-511 Crossref Scopus (0) PubMed Google Scholar
  4. [4]4. Baker, S.J. ∙ Reddy, E.P. Modulation of life and death by the TNF receptor superfamily Oncogene. 1998; 17:3261-3270 Crossref Scopus (486) PubMed Google Scholar
  5. [5]5. Belvin, M.P. ∙ Jin, Y. ∙ Anderson, K.V. Cactus protein degradation mediates Drosophila dorsal-ventral signaling Genes Dev. 1995; 9:783-793 Crossref Scopus (154) PubMed Google Scholar
  6. [6]6. Beramendi, A. ∙ Peron, S. ∙ Megighian, A. ... The inhibitor kappaB-ortholog Cactus is necessary for normal neuromuscular function in Drosophila melanogaster Neuroscience. 2005; 134:397-406 Full Text Full Text (PDF) Scopus (21) PubMed Google Scholar
  7. [9]9. Cantera, R. ∙ Kozlova, T. ∙ Barillas-Mury, C. ... Muscles and innveravtion are affected by loss of Dorsal in the fruit fly, Drosophila melanogaster Mol. Cell. Neurosci. 1999; 13:131-141 Crossref Scopus (28) PubMed Google Scholar
  8. [10]10. Cantera, R. ∙ Roos, E. ∙ Engstrom, Y. DIF and Cactus are colocalized in the larval nervous system of Drosophila melanogaster J. Neurobiol. 1999; 38:16-26 Crossref Scopus (24) PubMed Google Scholar
  9. [12]12. Eaton, B.A. ∙ Davis, G.W. LIM Kinase1 controls synaptic stability downstream of the type II BMP receptor Neuron. 2005; 47:695-708 Full Text Full Text (PDF) Scopus (145) PubMed Google Scholar
  10. [13]13. Edwards, D.N. ∙ Towb, P. ∙ Wasserman, S.A. An activity-dependent network of interactions links the Rel protein Dorsal with its cytoplasmic regulators Development. 1997; 124:3855-3864 Crossref PubMed Google Scholar
  11. [14]14. Evan, G.I. ∙ Lewis, G.K. ∙ Ramsay, G. ... Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product Mol. Cell. Biol. 1985; 5:3610-3616 Crossref Scopus (2370) PubMed Google Scholar
  12. [15]15. Featherstone, D.E. ∙ Rushton, E. ∙ Rohrhough, J. ... An essential Drosophila glutamate receptor subunit that functions in both central neuropil and neuromusclar junction J. Neurosci. 2005; 25:3199-3208 Crossref Scopus (105) PubMed Google Scholar
  13. [16]16. Flores-Saaib, R.D. ∙ Jia, S. ∙ Courey, A.J. Activation and repression by the C-terminal domain of Dorsal Development. 2001; 128:1869-1879 Crossref PubMed Google Scholar
  14. [17]17. Furukawa, K. ∙ Mattson, M.P. The transcription factor NF-kappaB mediates increases in calcium currents and decreases in NMDA- and AMPA/kainate-induced currents induced by tumor necrosis factor-alpha in hippocampal neurons J. Neurochem. 1998; 70:1876-1886 Crossref Scopus (228) PubMed Google Scholar
  15. [19]19. Ghosh, S. ∙ May, M.J. ∙ Kopp, E.B. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses Annu. Rev. Immunol. 1998; 16:225-260 Crossref Scopus (4717) PubMed Google Scholar
  16. [20]20. Gillespie, S.K. ∙ Wasserman, S.A. Dorsal, a Drosophila Rel-like protein, is phosphorylated upon activation of the transmembrane protein Toll Mol. Cell. Biol. 1994; 14:3559-3568 Crossref Scopus (87) PubMed Google Scholar
  17. [21]21. Govind, S. Rel signalling pathway and the melanotic tumour phenotype of Drosophila Biochem. Soc. Trans. 1996; 24:39-44 Crossref Scopus (22) PubMed Google Scholar
  18. [22]22. Govind, S. Control of development and immunity by rel transcription factors in Drosophila Oncogene. 1999; 18:6875-6887 Crossref Scopus (94) PubMed Google Scholar
  19. [23]23. Guttridge, D.C. ∙ Mayo, M.W. ∙ Madrid, L.V. ... NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia Science. 2000; 289:2363-2366 Crossref Scopus (794) PubMed Google Scholar
  20. [25]25. Halfon, M.S. ∙ Keshishian, H. The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo Dev. Biol. 1998; 199:164-174 Crossref Scopus (41) PubMed Google Scholar
  21. [26]26. Halfon, M.S. ∙ Hashimoto, C. ∙ Keshishian, H. The Drosophila toll gene functions zygotically and is necessary for proper motoneuron and muscle development Dev. Biol. 1995; 169:151-167 Crossref Scopus (88) PubMed Google Scholar
  22. [27]27. Hecht, P.M. ∙ Anderson, K.V. Genetic characterization of tube and pelle, genes required for signaling between Toll and dorsal in the specification of the dorsal-ventral pattern of the Drosophila embryo Genetics. 1993; 135:405-417 Crossref PubMed Google Scholar
  23. [28]28. Isoda, K. ∙ Nusslein-Volhard, C. Disulfide cross-linking in crude embryonic lysates reveals three complexes of the Drosophila morphogen dorsal and its inhibitor cactus Proc. Natl. Acad. Sci. USA. 1994; 91:5350-5354 Crossref Scopus (28) PubMed Google Scholar
  24. [29]29. Isoda, K. ∙ Roth, S. ∙ Nusslein-Volhard, C. The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants Genes Dev. 1992; 6:619-630 Crossref Scopus (47) PubMed Google Scholar
  25. [30]30. Kambris, Z. ∙ Hoffmann, J.A. ∙ Imler, J.L. ... Tissue and stage-specific expression of the Tolls in Drosophila embryos Gene Expr. Patterns. 2002; 2:311-317 Crossref Scopus (76) PubMed Google Scholar
  26. [31]31. Kauppila, S. ∙ Maaty, W.S. ∙ Chen, P. ... Eiger and its receptor, Wengen, comprise a TNF-like system in Drosophila Oncogene. 2003; 22:4860-4867 Crossref Scopus (142) PubMed Google Scholar
  27. [32]32. Ladner, K.J. ∙ Caligiuri, M.A. ∙ Guttridge, D.C. Tumor necrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products J. Biol. Chem. 2003; 278:2294-2303 Full Text Full Text (PDF) Scopus (203) PubMed Google Scholar
  28. [33]33. Manfruelli, P. ∙ Reichhart, J.M. ∙ Steward, R. ... A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF EMBO J. 1999; 18:3380-3391 Crossref Scopus (167) PubMed Google Scholar
  29. [34]34. Marrus, S.B. ∙ Portman, S.L. ∙ Allen, M.J. ... Differential Localization of glutamate receptor subunits at the Drosophila neuromuscular junction J. Neurosci. 2004; 24:1406-1415 Crossref Scopus (243) PubMed Google Scholar
  30. [35]35. Mattson, M.P. ∙ Camandola, S. NF-kappaB in neuronal plasticity and neurodegenerative disorders J. Clin. Invest. 2001; 107:247-254 Crossref Scopus (803) PubMed Google Scholar
  31. [36]36. Mattson, M.P. ∙ Culmsee, C. ∙ Yu, Z. ... Roles of nuclear factor kappaB in neuronal survival and plasticity J. Neurochem. 2000; 74:443-456 Crossref Scopus (438) PubMed Google Scholar
  32. [38]38. Meffert, M.K. ∙ Baltimore, D. Physiological functions for brain NF-kappaB Trends Neurosci. 2005; 28:37-43 Full Text Full Text (PDF) Scopus (267) PubMed Google Scholar
  33. [39]39. Meffert, M.K. ∙ Chang, J.M. ∙ Wiltgen, B.J. ... NF-kappa B functions in synaptic signaling and behavior Nat. Neurosci. 2003; 6:1072-1078 Crossref Scopus (605) PubMed Google Scholar
  34. [40]40. Moon, R.T. ∙ Bowerman, B. ∙ Boutros, M. ... The promise and perils of Wnt signaling through beta-catenin Science. 2002; 296:1644-1646 Crossref Scopus (905) PubMed Google Scholar
  35. [41]41. Nicolai, M. ∙ Lasbleiz, C. ∙ Dura, J.M. Gain-of-function screen identifies a role of the Src64 oncogene in Drosophila mushroom body development J. Neurobiol. 2003; 57:291-302 Crossref Scopus (42) PubMed Google Scholar
  36. [42]42. Nicolas, E. ∙ Reichhart, J.M. ∙ Hoffmann, J.A. ... In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila J. Biol. Chem. 1998; 273:10463-10469 Full Text Full Text (PDF) Scopus (89) PubMed Google Scholar
  37. [43]43. Norris, J.L. ∙ Manley, J.L. Selective nuclear transport of the Drosophila morphogen dorsal can be established by a signaling pathway involving the transmembrane protein Toll and protein kinase A Genes Dev. 1992; 6:1654-1667 Crossref Scopus (67) PubMed Google Scholar
  38. [44]44. Nose, A. ∙ Van Vactor, D. ∙ Auld, V. ... Development of neuromuscular specificity in Drosophila Cold Spring Harb. Symp. Quant. Biol. 1992; 57:441-449 Crossref PubMed Google Scholar
  39. [46]46. Pan, D.J. ∙ Huang, J.D. ∙ Courey, A.J. Functional analysis of the Drosophila twist promoter reveals a dorsal-binding ventral activator region Genes Dev. 1991; 5:1892-1901 Crossref Scopus (112) PubMed Google Scholar
  40. [47]47. Pan, D. ∙ Courey, A.J. The same dorsal binding site mediates both activation and repression in a context-dependent manner EMBO J. 1992; 11:1837-1842 Crossref Scopus (61) PubMed Google Scholar
  41. [48]48. Petersen, S.A. ∙ Fetter, R.D. ∙ Noordermeer, J.N. ... Genetic analysis of glutamate receptors in Drosophila reveals a retrograde signal regulating presynaptic transmitter release Neuron. 1997; 19:1237-1248 Full Text Full Text (PDF) Scopus (383) PubMed Google Scholar
  42. [49]49. Pielage, J. ∙ Fetter, R.D. ∙ Davis, G.W. A postsynaptic spectrin scaffold defines active zone size, spacing, and efficacy at the Drosophila neuromuscular junction J. Cell Biol. 2006; 175:491-503 Crossref Scopus (96) PubMed Google Scholar
  43. [50]50. Qin, G. ∙ Schwarz, T. ∙ Kittel, R.J. ... Four different subunits are essential for expressing the synaptic glutamate receptor at neuromusclar junctions of Drosophila J. Neurosci. 2005; 25:3209-3218 Crossref Scopus (166) PubMed Google Scholar
  44. [51]51. Qiu, P. ∙ Pan, P.C. ∙ Govind, S. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis Development. 1998; 125:1909-1920 Crossref PubMed Google Scholar
  45. [52]52. Rasse, T.M. ∙ Fouquet, W. ∙ Schmid, A. ... Glutamate receptor dynamics organizing synapse formation in vivo Nat. Neurosci. 2005; 8:898-905 Crossref Scopus (155) PubMed Google Scholar
  46. [53]53. Reach, M. ∙ Galindo, R.L. ∙ Towb, P. ... A gradient of Cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo Dev. Biol. 1996; 180:353-364 Crossref Scopus (102) PubMed Google Scholar
  47. [54]54. Roth, S. ∙ Stein, D. ∙ Nusslein-Volhard, C. A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo Cell. 1989; 59:1189-1202

Cited by

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Authors
Heckscher, E. S., Fetter, R. D., Marek, K. W., Albin, S. D., & Davis, G. W.
Affiliations
University of California, San Francisco (US)
Corresponding author
Davis, Graeme W.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2007-09
Volume
55
Issue
6
Pages
859-873
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2007.08.005
PMC
PMC2701504
OpenAlex
W2064196828
Cited by
72
References
5
Citations by year
2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 8 · 2016: 1 · 2015: 6 · 2014: 7 · 2013: 8 · 2012: 4
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (NS39313)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
NF-κB signaling, Dorsal, cactus, postsynaptic glutamate receptors, neuromuscular junction, Drosophila, postsynaptic density, post-transcriptional regulation, synaptic plasticity
MeSH terms
Alleles, Animals, Cytoplasm, Drosophila, Electrophysiology, Image Processing, Computer-Assisted, Immunohistochemistry, Membranes, Microscopy, Electron, Muscles, Mutation, Neuromuscular Junction, Protein Processing, Post-Translational, Synapses, Blotting, Western, NF-kappa B, Receptors, Glutamate, Reverse Transcriptase Polymerase Chain Reaction, I-kappa B Proteins, Interleukin-1 Receptor-Associated Kinases

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