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.

journal_name

Elife

journal_title

eLife

authors

Mahoney RE,Azpurua J,Eaton BA

doi

10.7554/eLife.16807

subject

Has Abstract

pub_date

2016-08-15 00:00:00

issn

2050-084X

journal_volume

5

pub_type

杂志文章

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