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PMID: 8893021 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of synapse structure and function by the Drosophila tumor suppressor gene dlg.

Neuron ·Vol. 17 ·No. 4 ·1996-10-00 ·Pages 627-40

Budnik V, Koh YH, Guan B, Hartmann B, Hough C, Woods D, Gorczyca M

Abstract

Mutations of the tumor suppressor gene discs-large (dlg) lead to postsynaptic structural defects. Here, we report that mutations in dlg also result in larger synaptic currents at fly neuromuscular junctions. By selectively targeting DLG protein to either muscles or motorneurons using Gal-4 enhancer trap lines, we were able to rescue substantially the reduced postsynaptic structure in mutants. Rescue of the physiological defect was accomplished by presynaptic, but not postsynaptic targeting, consistent with our finding that miniature excitatory junctional currents were not changed in dlg mutants. These results suggest that DLG functions in the regulation of neurotransmitter release and postsynaptic structure. We propose that DLG is an integral part of a mechanism by which changes in both neurotransmitter release and synapse structure are accomplished during development and plasticity.

MeSH Terms
Animals Axons Drosophila/genetics,physiology Drosophila Proteins Evoked Potentials Gene Expression Regulation, Developmental Genes, Insect Genes, Tumor Suppressor Insect Hormones/biosynthesis,genetics Microscopy, Electron Motor Neurons/physiology,ultrastructure Muscles/innervation Mutagenesis Neuromuscular Junction/physiology,ultrastructure Synapses/physiology,ultrastructure Synaptic Transmission Tumor Suppressor Proteins
Chemicals
Drosophila Proteins Insect Hormones Tumor Suppressor Proteins dlg1 protein, Drosophila
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Budnik V
Department of Biology, University of Massachusetts, Amherst 01003, USA.
Koh Y H
Guan B
Hartmann B
Hough C
Woods D
Gorczyca M
References (46)
46 references, click to expand
  1. Differential physiology and morphology of motor axons to ventral longitudinal muscles in larval Drosophila.
    J Comp Neurol. 1994 Dec 15;350(3):463-72 PMID: 7884051
  2. Differential ultrastructure of synaptic terminals on ventral longitudinal abdominal muscles in Drosophila larvae.
    J Neurobiol. 1993 Aug;24(8):1008-24 PMID: 8409966
  3. The Drosophila tumor suppressor gene dlg is required for normal synaptic bouton structure.
    Neuron. 1994 Oct;13(4):823-35 PMID: 7946331
  4. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
    Development. 1993 Jun;118(2):401-15 PMID: 8223268
  5. Synapse maturation and structural plasticity at Drosophila neuromuscular junctions.
    Curr Opin Neurobiol. 1996 Dec;6(6):858-67 PMID: 9000022
  6. Residual Ca2+ and short-term synaptic plasticity.
    Nature. 1994 Oct 13;371(6498):603-6 PMID: 7935792
  7. ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions.
    Mech Dev. 1993 Dec;44(2-3):85-9 PMID: 8155583
  8. Neurogenetic analysis of potassium currents in Drosophila: synergistic effects on neuromuscular transmission in double mutants.
    J Neurogenet. 1983 Sep;1(1):17-28 PMID: 6100303
  9. Synaptic development in the crayfish opener muscle.
    J Neurobiol. 1976 Jul;7(4):289-312 PMID: 956815
  10. Voltage clamp analysis of membrane currents in larval muscle fibers of Drosophila: alteration of potassium currents in Shaker mutants.
    J Neurosci. 1985 Oct;5(10):2626-40 PMID: 2413182
  11. Segmental peptidergic innervation of abdominal targets in larval and adult dipteran insects revealed with an antiserum against leucokinin I.
    Cell Tissue Res. 1992 Sep;269(3):459-71 PMID: 1423512
  12. Innervation directs receptor synthesis and localization in Drosophila embryo synaptogenesis.
    Nature. 1993 Jan 28;361(6410):350-3 PMID: 8426654
  13. Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases.
    Neuropharmacology. 1996;35(7):993-1000 PMID: 8938729
  14. The maternal effect of lethal(1)discs-large-1: a recessive oncogene of Drosophila melanogaster.
    Dev Biol. 1988 Jun;127(2):392-407 PMID: 3132409
  15. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions.
    Cell. 1991 Aug 9;66(3):451-64 PMID: 1651169
  16. Morphological plasticity of motor axons in Drosophila mutants with altered excitability.
    J Neurosci. 1990 Nov;10(11):3754-68 PMID: 1700086
  17. Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia.
    J Cell Biol. 1996 Sep;134(6):1469-82 PMID: 8830775
  18. Altered nerve terminal arborization and synaptic transmission in Drosophila mutants of cell adhesion molecule fasciclin I.
    J Neurosci. 1995 Oct;15(10):6679-87 PMID: 7472428
  19. Neuromuscular development in Drosophila: insights from single neurons and single genes.
    Trends Neurosci. 1993 Jul;16(7):278-83 PMID: 7689772
  20. Identification of the neuropeptide transmitter proctolin in Drosophila larvae: characterization of muscle fiber-specific neuromuscular endings.
    J Neurosci. 1988 Jan;8(1):242-55 PMID: 2892897
  21. Stereotypic morphology of glutamatergic synapses on identified muscle cells of Drosophila larvae.
    J Neurosci. 1989 Feb;9(2):710-25 PMID: 2563766
  22. Assembly of the postsynaptic apparatus.
    Curr Opin Neurobiol. 1995 Feb;5(1):62-7 PMID: 7773008
  23. Developmental mechanisms that generate precise patterns of neuronal connectivity.
    Cell. 1993 Jan;72 Suppl:77-98 PMID: 8428376
  24. Morphogenesis in memory formation: synaptic and cellular mechanisms.
    Behav Brain Res. 1995 Jan 23;66(1-2):1-6 PMID: 7755880
  25. Muscle development is independent of innervation during Drosophila embryogenesis.
    Development. 1993 Oct;119(2):533-43 PMID: 8287801
  26. L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction.
    J Physiol. 1976 Oct;262(1):215-36 PMID: 186587
  27. Building synapses: agrin and dystroglycan stick together.
    Trends Neurosci. 1994 Nov;17(11):469-73 PMID: 7531888
  28. Octopamine immunoreactivity in the fruit fly Drosophila melanogaster.
    J Comp Neurol. 1995 May 29;356(2):275-87 PMID: 7629319
  29. Quantal components of the end-plate potential.
    J Physiol. 1954 Jun 28;124(3):560-73 PMID: 13175199
  30. Age-dependent long-term adaptation of crayfish phasic motor axon synapses to altered activity.
    J Neurosci. 1985 Feb;5(2):459-67 PMID: 3973678
  31. Insulin-like receptor and insulin-like peptide are localized at neuromuscular junctions in Drosophila.
    J Neurosci. 1993 Sep;13(9):3692-704 PMID: 8366341
  32. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.
    Nature. 1995 Nov 2;378(6552):85-8 PMID: 7477295
  33. Control of X chromosome transcription by the maleless gene in Drosophila.
    Nature. 1980 Jun 19;285(5766):573-5 PMID: 7402300
  34. Isolation and expression of scabrous, a gene regulating neurogenesis in Drosophila.
    Genes Dev. 1990 Nov;4(11):1848-61 PMID: 2125959
  35. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.
    Science. 1995 Sep 22;269(5231):1737-40 PMID: 7569905
  36. Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein.
    J Neurosci. 1995 Mar;15(3 Pt 2):2354-66 PMID: 7891172
  37. Structural synaptic correlate of long-term potentiation: formation of axospinous synapses with multiple, completely partitioned transmission zones.
    Hippocampus. 1993 Oct;3(4):435-45 PMID: 8269035
  38. Ultrastructure of neuromuscular junctions in Drosophila: comparison of wild type and mutants with increased excitability.
    J Neurobiol. 1993 Aug;24(8):1025-44 PMID: 8409967
  39. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein.
    Neuron. 1992 Nov;9(5):929-42 PMID: 1419001
  40. Presynaptic inhibition at the crayfish neuromuscular junction.
    J Physiol. 1961 Mar;155:543-62 PMID: 13724752
  41. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins.
    Neuron. 1996 Jul;17 (1):103-13 PMID: 8755482
  42. Synaptic structure and development: the neuromuscular junction.
    Cell. 1993 Jan;72 Suppl:99-121 PMID: 8428377
  43. The Drosophila tumor suppressor gene, dlg, is involved in structural plasticity at a glutamatergic synapse.
    Curr Biol. 1996 Jun 1;6(6):695-706 PMID: 8793296
  44. SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A.
    J Biol Chem. 1993 Mar 5;268(7):4580-3 PMID: 7680343
  45. Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ.
    Cell. 1996 Jun 28;85(7):1067-76 PMID: 8674113
  46. Long-term potentiation and activity-dependent retinotopic sharpening in the regenerating retinotectal projection of goldfish: common sensitive period and sensitivity to NMDA blockers.
    J Neurosci. 1990 Jan;10(1):233-46 PMID: 2153773
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
Published
1996-10-00
Pages
627-40
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC4661176
Subset
IM
Grants
NINDS NIH HHS · R01 NS030072 · United States
NINDS NIH HHS · R21 NS070032 · United States
NINDS NIH HHS · K04 NS01786 · United States
NINDS NIH HHS · R01 NS70032 · United States
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