title: TOR is required for the retrograde regulation of synaptic homeostasis at the Drosophila neuromuscular junction.
abstract: Homeostatic mechanisms operate to stabilize synaptic function; however, we know little about how they are regulated. Exploiting Drosophila genetics, we have uncovered a critical role for the target of rapamycin (TOR) in the regulation of synaptic homeostasis at the Drosophila larval neuromuscular junction. Loss of postsynaptic TOR disrupts a retrograde compensatory enhancement in neurotransmitter release that is normally triggered by a reduction in postsynaptic glutamate receptor activity. Moreover, postsynaptic overexpression of TOR or a phosphomimetic form of S6 ribosomal protein kinase, a common target of TOR, can trigger a strong retrograde increase in neurotransmitter release. Interestingly, heterozygosity for eIF4E, a critical component of the cap-binding protein complex, blocks the retrograde signal in all these cases. Our findings suggest that cap-dependent translation under the control of TOR plays a critical role in establishing the activity dependent homeostatic response at the NMJ.
authors.affiliation: Department of Physiology, McGill University, Montréal, QC H3G 1Y6, Canada.
authors.forename: Jay
authors.initials: J
authors.lastname: Penney
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsurudome
authors.forename: Edward H
authors.initials: EH
authors.lastname: Liao
authors.forename: Fatima
authors.initials: F
authors.lastname: Elazzouzi
authors.forename: Mark
authors.initials: M
authors.lastname: Livingstone
authors.forename: Miranda
authors.initials: M
authors.lastname: Gonzalez
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: A Pejmun
authors.initials: AP
authors.lastname: Haghighi
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007814:Larva / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D009469:Neuromuscular Junction / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D017470:Receptors, Glutamate; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases