title: Acute induction of conserved synaptic signaling pathways in Drosophila melanogaster.
abstract: Analyses of early molecular and cellular events associated with long-term plasticity remain hampered in Drosophila by the lack of an acute procedure to activate signal transduction pathways, gene expression patterns, and other early cellular events associated with long-term synaptic change. Here we describe the development and first use of such a technique. Bursts of neural activity induced in Drosophila comatosets and CaP60A Kumts mutants, with conditional defects in N-ethylmaleimide-sensitive fusion factor 1 and sarco-endoplasmic reticulum Ca2+ ATPase, respectively, result in persistent (>4 hr) activation of neuronal extracellular signal-regulated kinase (ERK). ERK activation at the larval neuromuscular junction coincides with rapid reduction of synaptic Fasciclin II; in soma, nuclear translocation of activated ERK occurs together with increased transcription of the immediate-early genes Fos and c/EBP (CCAAT element binding protein). The effect of "seizure-stimulation" on ERK activation requires neural activity and is mediated through activation of MEK (MAPK/erk kinase), the MAPKK (mitogen-activated protein kinase kinase) that functions upstream of ERK. Our results (1) provide direct proof for the conservation of synaptic signaling pathways in arthropods, (2) demonstrate the utility of a new genetic tool for analysis of synaptic plasticity in Drosophila, and (3) potentially enable new proteomic and genomic analyses of activity-regulated molecules in an important model organism.
authors.affiliation: Department of Molecular and Cellular Biology and Arizona Research Labs Division of Neurobiology, University of Arizona, Tucson, Arizona 85721, USA. choeffer@u.arizona.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Hoeffer
authors.forename: S
authors.initials: S
authors.lastname: Sanyal
authors.forename: M
authors.initials: M
authors.lastname: Ramaswami
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002467:Cell Nucleus / Q000000981:diagnostic imaging* / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D005786:Gene Expression Regulation; D007814:Larva; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D052066:N-Ethylmaleimide-Sensitive Proteins; D009469:Neuromuscular Junction / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010243:Paralysis / Q000503:physiopathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012640:Seizures / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D013696:Temperature; D014463:Ultrasonography; D033921:Vesicular Transport Proteins
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D033921:Vesicular Transport Proteins; C498732:comt protein, Drosophila; C051642:fasciclin II; C435749:kay protein, Drosophila; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D052066:N-Ethylmaleimide-Sensitive Proteins; D000252:Calcium-Transporting ATPases