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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism
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Calcium-Transporting ATPases / genetics
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Carrier Proteins / genetics
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Nucleus / diagnostic imaging*
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Cell Nucleus / metabolism
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Central Nervous System / cytology
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Central Nervous System / physiology
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Drosophila melanogaster / physiology*
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Gene Expression Regulation
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Larva
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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N-Ethylmaleimide-Sensitive Proteins
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Neuromuscular Junction / physiology
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Neuronal Plasticity / physiology
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Neurons / metabolism
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Neurons / physiology
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Paralysis / physiopathology
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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Seizures / physiopathology
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Signal Transduction / physiology*
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Synapses / metabolism
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Synapses / physiology*
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Temperature
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Ultrasonography
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Vesicular Transport Proteins*
Substances
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CCAAT-Enhancer-Binding Proteins
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Carrier Proteins
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Cell Adhesion Molecules, Neuronal
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Drosophila Proteins
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Vesicular Transport Proteins
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comt protein, Drosophila
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fasciclin II
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kay protein, Drosophila
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Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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N-Ethylmaleimide-Sensitive Proteins
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Calcium-Transporting ATPases