Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery

Rebekah Elizabeth Mahoney, Jorge Azpurua, Benjamin A Eaton

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere16807
JournaleLife
Volume5
Issue numberAUGUST
DOIs
StatePublished - Aug 15 2016

Fingerprint

Synaptic Transmission
Machinery
Carrier Proteins
Insulin
Synaptic Vesicles
Drosophila
Neurodegenerative diseases
Exocytosis
Neurology
Motor Neurons
Neurodegenerative Diseases
Synapses
Nervous System
Neurons
Neurotransmitter Agents
Proteins
Fusion reactions
Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery. / Mahoney, Rebekah Elizabeth; Azpurua, Jorge; Eaton, Benjamin A.

In: eLife, Vol. 5, No. AUGUST, e16807, 15.08.2016.

Research output: Contribution to journalArticle

Mahoney, Rebekah Elizabeth ; Azpurua, Jorge ; Eaton, Benjamin A. / Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery. In: eLife. 2016 ; Vol. 5, No. AUGUST.
@article{959b9ad79d66432f9e91ac7166fa11b6,
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.",
author = "Mahoney, {Rebekah Elizabeth} and Jorge Azpurua and Eaton, {Benjamin A}",
year = "2016",
month = "8",
day = "15",
doi = "10.7554/eLife.16807",
language = "English (US)",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "AUGUST",

}

TY - JOUR

T1 - Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery

AU - Mahoney, Rebekah Elizabeth

AU - Azpurua, Jorge

AU - Eaton, Benjamin A

PY - 2016/8/15

Y1 - 2016/8/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84986181782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986181782&partnerID=8YFLogxK

U2 - 10.7554/eLife.16807

DO - 10.7554/eLife.16807

M3 - Article

C2 - 27525480

AN - SCOPUS:84986181782

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

IS - AUGUST

M1 - e16807

ER -