Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants
| Autor: | William G. Quinn, Zhuo Guan, Lauren K Buhl, J. Troy Littleton |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Littleton, J. Troy, Guan, Zhuo, Buhl, Lauren Kaye, Quinn, William G. |
| Rok vydání: | 2011 |
| Předmět: |
Cognitive Neuroscience
Blotting Western Mutant Gene Expression medicine.disease_cause Adenylyl cyclase Cellular and Molecular Neuroscience chemistry.chemical_compound Memory medicine Animals Drosophila Proteins Learning Oligonucleotide Array Sequence Analysis Regulation of gene expression Mutation Neuronal Plasticity biology Reverse Transcriptase Polymerase Chain Reaction Research Neuropeptides Phosphoproteins biology.organism_classification Immunohistochemistry Associative learning Drosophila melanogaster Neuropsychology and Physiological Psychology Gene Expression Regulation chemistry Synapses Microscopy Electron Scanning Signal transduction Neuroscience Drosophila Protein Adenylyl Cyclases Signal Transduction |
| Zdroj: | Littleton |
| ISSN: | 1549-5485 |
| DOI: | 10.1101/lm.2027111 |
| Popis: | Genetic studies in Drosophila have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in radish (rsh) mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways leading to these forms of memory may share the cAMP cascade critical for associative learning. Dunce, which encodes a cAMP-specific phosphodiesterase, and rutabaga, which encodes an adenylyl cyclase, both disrupt short-term memory. Amnesiac encodes a pituitary adenylyl cyclase-activating peptide homolog and is required for middle-term memory. Here, we demonstrate that the Radish protein localizes to the cytoplasm and nucleus and is a PKA phosphorylation target in vitro. To characterize how these plasticity pathways may manifest at the synaptic level, we assayed synaptic connectivity and performed an expression analysis to detect altered transcriptional networks in rutabaga, dunce, amnesiac, and radish mutants. All four mutants disrupt specific aspects of synaptic connectivity at larval neuromuscular junctions (NMJs). Genome-wide DNA microarray analysis revealed ∼375 transcripts that are altered in these mutants, suggesting defects in multiple neuronal signaling pathways. In particular, the transcriptional target Lapsyn, which encodes a leucine-rich repeat cell adhesion protein, localizes to synapses and regulates synaptic growth. This analysis provides insights into the Radish-dependent ARM pathway and novel transcriptional targets that may contribute to memory processing in Drosophila. National Institutes of Health (U.S.) (Grant no. NS43244) |
| Databáze: | OpenAIRE |
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