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Targeted expression of truncated glued disrupts giant fiber synapse formation in Drosophila

By Marcus James Allen, Xiaoliang Shan, Phyllis Caruccio, Stephan J. Froggett, Kevin G. Moffat and R. K. Murphey

Abstract

Glued1 (Gl1) mutants produce a truncated protein that acts as a poison subunit and disables the cytoplasmic retrograde motor dynein. Heterozygous mutants have axonal defects in the adult eye and the nervous system. Here we show that selective expression of the poison subunit in neurons of the giant fiber (GF) system disrupts synaptogenesis between the GF and one of its targets, the tergotrochanteral motorneuron (TTMn). Growth and pathfinding by the GF axon and the TTMn dendrite are normal, but the terminal of the GF axon fails to develop normally and becomes swollen with large vesicles. This is a presynaptic defect because expression of truncated Glued restricted to the GF results in the same defect. When tested electrophysiologically, the flies with abnormal axons show a weakened or absent GF-TTMn connection. In Glued1 heterozygotes, GF-TTMn synapse formation appears morphologically normal, but adult flies show abnormal responses to repetitive stimuli. This physiological effect is also observed when tetanus toxin is expressed in the GFs. Because the GF-TTMn is thought to be a mixed electrochemical synapse, the results show that Glued has a role in assembling both the chemical and electrical components. We speculate that disrupting transport of a retrograde signal disrupts synapse formation and maturation

Topics: QL, RC0321
Publisher: Society for Neuroscience
Year: 1999
OAI identifier: oai:wrap.warwick.ac.uk:2996

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Citations

  1. (1999). 19(21):9374–9384 9383Hollenbeck PJ,
  2. (1985). A doi
  3. (1990). A deficiency chromosome in Drosophila alters neuritic projections in an identified motoneuron. doi
  4. (1982). A mutation in Drosophila alters normal connectivity between two identified neurons. doi
  5. (1995). Affinity-chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex. doi
  6. (1996). Altered habituation of an identified escape circuit in Drosophila memory mutants.
  7. (1997). An NGF-TrkAmediated retrograde signal to transcription factor CREB in sympathetic neurons.
  8. (1983). Analysis of visual system development in Drosophila melanogaster: mutations at the Glued locus. doi
  9. (1980). Anatomy of the giant fiber pathway in Drosophila. I. Three thoracic components of the pathway. doi
  10. (1999). Controlling the motor neuron. doi
  11. (1998). Cytoplasmic dynein and dynactin are required for the transport of microtubules into the axon. doi
  12. (1995). Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and Pl50(Glued). doi
  13. (1998). Development of the giant fiber neuron of Drosophila melanogaster. doi
  14. (1993). Dror, a potential neurotrophic receptor gene, encodes a Drosophila homolog of the vertebrate Ror family of Trk-related receptor tyrosine kinases. doi
  15. (1999). Dynein–dynactin function and sensory axon growth during Drosophila metamorphosis: a role for retrograde motors. doi
  16. (1992). Effects of kinesin mutations on neuronal functions. doi
  17. (1997). Glued participates in distinct microtubulebased activities in Drosophila eye development.
  18. (1981). Heavy metal intensification of DAB-based HRP reaction product. doi
  19. (1984). Identification of a cholinergic synapse in the giant fiber pathway of Drosophila using conditional mutations of acetylcholine synthesis. doi
  20. (1998). Kinesin and dynein superfamily proteins and the mechanism of organelle transport. doi
  21. (1998). Kinesin light chains are essential for axonal transport in Drosophila.
  22. (1996). Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila. Genetics 144:1075–1085.
  23. (1994). Long-term regulation of short-term release properties: retrograde signaling and synaptic development. Trends Neurosci 17:9–13. doi
  24. (1995). Making the connection: cytoskeletal rearrangements during growth cone guidance. doi
  25. (1999). Microtubules and neuronal polarity: lessons from mitosis. doi
  26. (1991). Molecular motors in the nervous system. doi
  27. (1980). Motor outputs of giant nerve fiber in Drosophila.
  28. (1996). Motor proteins: a dynamic duo. doi
  29. (1997). Mutant molecular motors disrupt neural circuits in Drosophila. doi
  30. (1996). Mutation of the axonal transport motor kinesin enhances paralytic and suppresses Shaker in Drosophila.
  31. (1984). Mutations altering synaptic connectivity between identified neurons in Drosophila.
  32. (1996). Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system.
  33. (1996). Mutations in the 8 kDa dynein light-chain gene disrupt sensory axon projections in the Drosophila imaginal CNS.
  34. (1992). Neurotrophic factorlike activity in Drosophila. doi
  35. (1994). NGF and the local control of nerve terminal growth. doi
  36. (1983). Normal and mutant connectivity between identified neurons in Drosophila. Trends Neurosci 6:214–219. doi
  37. (1999). Null mutation in shaking-B eliminates electrical, but not chemical, synapses in the Drosophila giant fiber system: a structural study. doi
  38. (1995). Regulation of cytoplasmic dynein function in-vivo by the Drosophila Glued complex.
  39. (1998). Regulation of synaptic depression rates in the cricket cercal sensory system.
  40. (1996). Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. doi
  41. (1981). Staging the metamorphosis of Drosophila melanogaster.
  42. (1995). Targeted expression of tetanus toxin light-chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. doi
  43. (1993). Targeted gene-expression as a means of altering cell fates and generating dominant phenotypes.
  44. (1983). The effect of chromosomal position on the expression of the Drosophila xanthine dehydrogenase gene. doi
  45. (1997). The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. doi
  46. (1994). The motor neurons innervating the direct flight muscles of Drosophila melanogaster are morphologically specialized. doi
  47. (1996). The product of the Drosophila gene, Glued, is the functional homolog of the P150(Glued) component of the vertebrate dynactin complex. doi
  48. (1998). The role of the dynactin complex in intracellular motility. Int Rev Cytol 182:69–109. doi
  49. (1997). The shaking-B2 mutation disrupts electrical synapses in a flight circuit in adult Drosophila.
  50. (1989). The spatial and temporal expression pattern of sevenless is exclusively controlled by gene-internal elements.

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