title: Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery.
abstract: 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.
authors.affiliation: Department of Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, United States.|Barshop Institute of Aging and Longevity Studies, University of Texas Health Sciences Center at San Antonio, San Antonio, United States.
authors.forename: Rebekah Elizabeth
authors.initials: RE
authors.lastname: Mahoney
authors.affiliation: Department of Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, United States.
authors.forename: Jorge
authors.initials: J
authors.lastname: Azpurua
authors.affiliation: Department of Physiology, University of Texas Health Sciences Center at San Antonio, San Antonio, United States.|Barshop Institute of Aging and Longevity Studies, University of Texas Health Sciences Center at San Antonio, San Antonio, United States.
authors.forename: Benjamin A
authors.identifier: 0000-0002-9807-5566
authors.initials: BA
authors.lastname: Eaton
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D005089:Exocytosis; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010448:Peptide Initiation Factors / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010448:Peptide Initiation Factors; C410006:Thor protein, Drosophila; C000605369:cpx protein, Drosophila
keywords: Complexin; D. melanogaster; FOXO; Staufen; neuroscience; neurotransmission; protein translation