@article {4523, title = {Arouser reveals a role for synapse number in the regulation of ethanol sensitivity.}, journal = {Neuron}, volume = {70}, year = {2011}, month = {2011 Jun 9}, pages = {979-90}, abstract = {

A reduced sensitivity to the sedating effects of alcohol is a characteristic associated with alcohol use disorders (AUDs). A genetic screen for ethanol sedation mutants in Drosophila identified arouser (aru), which functions in developing neurons to reduce ethanol sensitivity. Genetic evidence suggests that aru regulates ethanol sensitivity through its activation by Egfr/Erk signaling and its inhibition by PI3K/Akt signaling. The aru mutant also has an increased number of synaptic terminals in the larva and adult fly. Both the increased ethanol sensitivity and synapse number of the aru mutant are restored upon adult social isolation, suggesting a causal relationship between synapse number and ethanol sensitivity. We thus show that a developmental abnormality affecting synapse number and ethanol sensitivity is not permanent and can be reversed by manipulating the environment of the adult fly.

}, keywords = {Adaptor Proteins, Animal, Animals, Arabidopsis Proteins, Behavior, Brain, Central Nervous System Depressants, Developmental, Drosophila, Drosophila Proteins, Epidermal Growth Factor, Ethanol, Gene Expression Regulation, Genetically Modified, Green Fluorescent Proteins, Invertebrate Peptide, Larva, Mutation, Neuromuscular Junction, Neurons, Phosphatidylinositol 3-Kinases, Receptor, Receptors, Reflex, RNA Interference, Signal Transducing, Signal Transduction, Social Isolation, Synapses}, issn = {1097-4199}, doi = {10.1016/j.neuron.2011.03.030}, author = {Eddison, Mark and Guarnieri, Douglas J and Cheng, Ling and Liu, Che-Hsiung and Moffat, Kevin G and Davis, Graeme and Heberlein, Ulrike} } @article {46425, title = {Glial-derived prodegenerative signaling in the Drosophila neuromuscular system.}, journal = {Neuron}, volume = {72}, year = {2011}, month = {2011 Dec 8}, pages = {760-75}, abstract = {

We provide evidence for a prodegenerative, glial-derived signaling framework in the Drosophila neuromuscular system that includes caspase and mitochondria-dependent signaling. We demonstrate that Drosophila TNF-α (eiger) is expressed in a subset of peripheral glia, and the TNF-α receptor (TNFR), Wengen, is expressed in motoneurons. NMJ degeneration caused by disruption of the spectrin/ankyrin skeleton is suppressed by an eiger mutation or by eiger knockdown within a subset of peripheral glia. Loss of wengen in motoneurons causes a similar suppression providing evidence for glial-derived prodegenerative TNF-α signaling. Neither JNK nor NFκβ is required for prodegenerative signaling. However, we provide evidence for the involvement of both an initiator and effector caspase, Dronc and Dcp-1, and mitochondrial-dependent signaling. Mutations that deplete the axon and nerve terminal of mitochondria suppress degeneration as do mutations in Drosophila Bcl-2 (debcl), a mitochondria-associated protein, and Apaf-1 (dark), which links mitochondrial signaling with caspase activity in other systems.

}, keywords = {Animals, Animals, Genetically Modified, Apoptotic Protease-Activating Factor 1, Caspases, Disease Models, Animal, Drosophila, Drosophila Proteins, Excitatory Postsynaptic Potentials, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, Mitochondria, Motor Neuron Disease, Mutation, Nerve Degeneration, Nerve Tissue Proteins, Neuroglia, Neuromuscular Junction, Proto-Oncogene Proteins, Receptors, Tumor Necrosis Factor, RNA Interference, Signal Transduction}, issn = {1097-4199}, doi = {10.1016/j.neuron.2011.09.031}, author = {Keller, Lani C and Cheng, Ling and Locke, Cody J and M{\"u}ller, Martin and Fetter, Richard D and Davis, Graeme W} } @article {46419, title = {A presynaptic giant ankyrin stabilizes the NMJ through regulation of presynaptic microtubules and transsynaptic cell adhesion.}, journal = {Neuron}, volume = {58}, year = {2008}, month = {2008 Apr 24}, pages = {195-209}, abstract = {

In a forward genetic screen for mutations that destabilize the neuromuscular junction, we identified a novel long isoform of Drosophila ankyrin2 (ank2-L). We demonstrate that loss of presynaptic Ank2-L not only causes synapse disassembly and retraction but also disrupts neuronal excitability and NMJ morphology. We provide genetic evidence that ank2-L is necessary to generate the membrane constrictions that normally separate individual synaptic boutons and is necessary to achieve the normal spacing of subsynaptic protein domains, including the normal organization of synaptic cell adhesion molecules. Mechanistically, synapse organization is correlated with a lattice-like organization of Ank2-L, visualized using extended high-resolution structured-illumination microscopy. The stabilizing functions of Ank2-L can be mapped to the extended C-terminal domain that we demonstrate can directly bind and organize synaptic microtubules. We propose that a presynaptic Ank2-L lattice links synaptic membrane proteins and spectrin to the underlying microtubule cytoskeleton to organize and stabilize the presynaptic terminal.

}, keywords = {Amino Acid Motifs, Animals, Animals, Genetically Modified, Ankyrins, Cell Adhesion Molecules, Neuronal, Drosophila, Drosophila Proteins, Gene Expression Regulation, Horseradish Peroxidase, Larva, Luminescent Proteins, Microscopy, Electron, Transmission, Microtubules, Mutation, Neuromuscular Junction, Presynaptic Terminals, Synapsins, Synaptic Transmission}, issn = {1097-4199}, doi = {10.1016/j.neuron.2008.02.017}, author = {Pielage, Jan and Cheng, Ling and Fetter, Richard D and Carlton, Pete M and Sedat, John W and Davis, Graeme W} }