Ethanol stimulates the in vivo axonal movement of neuropeptide dense-core vesicles in Drosophila motor neurons

J Neurochem. 2018 Feb;144(4):466-482. doi: 10.1111/jnc.14230. Epub 2017 Oct 18.

Abstract

Proper neuronal function requires essential biological cargoes to be packaged within membranous vesicles and transported, intracellularly, through the extensive outgrowth of axonal and dendritic fibers. The precise spatiotemporal movement of these cargoes is vital for neuronal survival and, thus, is highly regulated. In this study we test how the axonal movement of a neuropeptide-containing dense-core vesicle (DCV) responds to alcohol stressors. We found that ethanol induces a strong anterograde bias in vesicle movement. Low doses of ethanol stimulate the anterograde movement of neuropeptide-DCV while high doses inhibit bi-directional movement. This process required the presence of functional kinesin-1 motors as reduction in kinesin prevented the ethanol-induced stimulation of the anterograde movement of neuropeptide-DCV. Furthermore, expression of inactive glycogen synthase kinase 3 (GSK-3β) also prevented ethanol-induced stimulation of neuropeptide-DCV movement, similar to pharmacological inhibition of GSK-3β with lithium. Conversely, inhibition of PI3K/AKT signaling with wortmannin led to a partial prevention of ethanol-stimulated transport of neuropeptide-DCV. Taken together, we conclude that GSK-3β signaling mediates the stimulatory effects of ethanol. Therefore, our study provides new insight into the physiological response of the axonal movement of neuropeptide-DCV to exogenous stressors. Cover Image for this Issue: doi: 10.1111/jnc.14165.

Keywords: Drosophila; atrial natriuretic peptide; dense-core vesicle transport; ethanol; glycogen synthase kinase 3β.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axonal Transport / drug effects*
  • Axons / drug effects
  • Axons / metabolism*
  • Central Nervous System Depressants / pharmacology*
  • Drosophila / physiology*
  • Ethanol / pharmacology*
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Immunohistochemistry
  • Kinesin / physiology
  • Larva
  • Lithium / pharmacology
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Signal Transduction / drug effects
  • Stimulation, Chemical
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism*
  • Wortmannin / pharmacology

Substances

  • Central Nervous System Depressants
  • Neuropeptides
  • Phosphoinositide-3 Kinase Inhibitors
  • Ethanol
  • Lithium
  • Glycogen Synthase Kinase 3 beta
  • Kinesin
  • Wortmannin