title: Targeted expression of truncated glued disrupts giant fiber synapse formation in Drosophila.
abstract: Glued(1) (Gl(1)) 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 Glued(1) 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.
authors.affiliation: Department of Biology, Morrill Science Center, University of Massachusetts, Amherst, Massachusetts 01003, USA. mjallen@bio.umass.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Allen
authors.forename: X
authors.initials: X
authors.lastname: Shan
authors.forename: P
authors.initials: P
authors.lastname: Caruccio
authors.forename: S J
authors.initials: SJ
authors.lastname: Froggett
authors.forename: K G
authors.initials: KG
authors.lastname: Moffat
authors.forename: R K
authors.initials: RK
authors.lastname: Murphey
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D004558:Electric Stimulation; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D016296:Mutagenesis; D009412:Nerve Fibers / Q000502:physiology*; D009420:Nervous System / Q000254:growth & development; D009424:Nervous System Physiological Phenomena; D017384:Sequence Deletion; D013569:Synapses / Q000502:physiology*
chemical_list: C105393:DCTN1-p150 protein, Drosophila; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins