Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell autonomous insulin signaling within the Drosophila CM9 motor neuron regulates the release of neurotransmitter via alteration of the synaptic vesicle fusion machinery. This effect of insulin utilizes the FOXO-dependent regulation of the thor gene, which encodes the Drosophila homologue of the eif-4e binding protein (4eBP). A critical target of this regulatory mechanism is Complexin, a synaptic protein known to regulate synaptic vesicle exocytosis. We find that the amounts of Complexin protein observed at the synapse is regulated by insulin and genetic manipulations of Complexin levels support the model that increased synaptic Complexin reduces neurotransmission in response to insulin signaling.
Pubmed ID: 27525480 RIS Download
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A national mouse monoclonal antibody generating resource for biochemical and immunohistochemical applications in mammalian brain. NeuroMabs are generated from mice immunized with synthetic and recombinant immunogens corresponding to components of the neuronal proteome as predicted from genomic and other large-scale cloning efforts. Comprehensive biochemical and immunohistochemical analyses of human, primate and non-primate mammalian brain are incorporated into the initial NeuroMab screening procedure. This yields a subset of mouse mAbs that are optimized for use in brain (i.e. NeuroMabs): for immunocytochemical-based imaging studies of protein localization in adult, developing and pathological brain samples, for biochemical analyses of subunit composition and post-translational modifications of native brain proteins, and for proteomic analyses of native brain protein networks. The NeuroMab facility was initially funded with a five-year U24 cooperative grant from NINDS and NIMH. The initial goal of the facility for this funding period is to generate a library of novel NeuroMabs against neuronal proteins, initially focusing on membrane proteins (receptors/channels/transporters), synaptic proteins, other neuronal signaling molecules, and proteins with established links to disease states. The scope of the facility was expanded with supplements from the NIH Blueprint for Neuroscience Research to include neurodevelopmental targets, the NIH Roadmap for Medical Research to include epigenetics targets, and NIH Office of Rare Diseases Research to include rare disease targets. These NeuroMabs will then be produced on a large scale and made available to the neuroscience research community on an inexpensive basis as tissue culture supernatants or purified immunoglobulin by Antibodies Inc. The UC Davis/NIH NeuroMab Facility makes NeuroMabs available directly to end users and is unable to accommodate sales to distributors for third party distribution. Note, NeuroMab antibodies are now offered through antibodiesinc.
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View all literature mentionsCollects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.
View all literature mentionsDigital microscopy software for research microscopy. It comes standard with drivers to control numerous instruments in and around the microscope. When online, data is acquired in a native-3D format over time, color and specimen locations in customizable experiment protocols. Data can be analyzed by a wide variety of tools for image processing including mathematical operations, statistics functions, analysis scripting and import to/export from MATLAB. Additional modules are available for special applications ranging from deconvolution to photomanipulation to multiphoton.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; wg[Sp-1]/CyO, P{Wee-P.ph0}Bacc[Wee-P20]; P{y[+t7.7] w[+mC]=20XUAS-6XmCherry-HA}attP2 from BDSC.
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View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis monoclonal targets DLG-1 (Disks Large)
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01764}attP2 from BDSC.
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View all literature mentionsThis monoclonal targets DLG-1 (Disks Large)
View all literature mentionsThis monoclonal targets DLG-1 (Disks Large)
View all literature mentionsThis monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsThis polyclonal targets Phospho-IGF-I Receptor beta (Tyr1131)/Insulin Receptor beta (Tyr1146)
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01764}attP2 from BDSC.
View all literature mentionsThis polyclonal targets Drosophila p70 S6 Kinase, phospho (Thr398)
View all literature mentionsThis monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsThis polyclonal targets Drosophila p70 S6 Kinase, phospho (Thr398)
View all literature mentionsDrosophila melanogaster with name w[1118]; foxo[Delta94]/TM6B, Tb[1] from BDSC.
View all literature mentionsThis polyclonal targets Phospho-IGF-I Receptor beta (Tyr1131)/Insulin Receptor beta (Tyr1146)
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsThis polyclonal targets Phospho-Drosophila Akt (Ser505)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis polyclonal targets Phospho-Drosophila Akt (Ser505)
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsDrosophila melanogaster with name w[1118]; foxo[Delta94]/TM6B, Tb[1] from BDSC.
View all literature mentionsBiomaterial supply resource which collects, maintains, and distributes independent transgenic fly lines. Most of the 38,000 fly lines are RNAi lines, but VDRC also maintains a collection of enhancer-GAL4 driver lines. Nearly all lines are in duplicate. Users can search for the stocks or DNA constructs for the gene of interest by entering CG number, synonym, or Transformant ID.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01764}attP2 from BDSC.
View all literature mentionsBiomaterial supply resource which collects, maintains, and distributes independent transgenic fly lines. Most of the 38,000 fly lines are RNAi lines, but VDRC also maintains a collection of enhancer-GAL4 driver lines. Nearly all lines are in duplicate. Users can search for the stocks or DNA constructs for the gene of interest by entering CG number, synonym, or Transformant ID.
View all literature mentions