Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery
- University of Texas Health Sciences Center at San Antonio, United States
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.
Article and author information
Author details
Funding
National Institute on Aging (T32-AG021890)
- Rebekah Elizabeth Mahoney
National Institutes of Health (NS062811)
- Benjamin Eaton
Lawrence Ellison Foundation (AG-NS-0415-07)
- Benjamin Eaton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kristin Scott, University of California, Berkeley, United States
Version history
- Received: April 8, 2016
- Accepted: August 14, 2016
- Accepted Manuscript published: August 15, 2016 (version 1)
- Accepted Manuscript updated: August 19, 2016 (version 2)
- Version of Record published: September 6, 2016 (version 3)
Copyright
© 2016, Mahoney et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery
eLife 5:e16807.
https://doi.org/10.7554/eLife.16807
