Functional and anatomical identification of a vesicular transporter mediating neuronal ATP release

Max Larsson, Keisuke Sawada, Cecilie Morland, Miki Hiasa, Lasse Ormel, Yoshinori Moriyama, Vidar Gundersen

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Abstract

ATP is known to be coreleased with glutamate at certain central synapses. However, the nature of its release is controversial. Here, we demonstrate that ATP release from cultured rat hippocampal neurons is sensitive to RNAi-mediated knockdown of the recently identified vesicular nucleotide transporter (VNUT or SLC17A9). In the intact brain, light microscopy showed particularly strong VNUT immunoreactivity in the cerebellar cortex, the olfactory bulb, and the hippocampus. Using immunoelectron microscopy, we found VNUT immunoreactivity colocalized with synaptic vesicles in excitatory and inhibitory terminals in the hippocampal formation. Moreover, VNUT immunolabeling, unlike that of the vesicular glutamate transporter VGLUT1, was enriched in preterminal axons and present in postsynaptic dendritic spines. Immunoisolation of synaptic vesicles indicated presence of VNUT in a subset of VGLUT1-containing vesicles. Thus, we conclude that VNUT mediates transport of ATP into synaptic vesicles of hippocampal neurons, thereby conferring a purinergic phenotype to these cells.

Original languageEnglish
Pages (from-to)1203-1214
Number of pages12
JournalCerebral Cortex
Volume22
Issue number5
DOIs
Publication statusPublished - May 2012

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Keywords

  • exocytosis
  • neurotransmitter
  • purinergic
  • ultrastructure
  • uptake

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Larsson, M., Sawada, K., Morland, C., Hiasa, M., Ormel, L., Moriyama, Y., & Gundersen, V. (2012). Functional and anatomical identification of a vesicular transporter mediating neuronal ATP release. Cerebral Cortex, 22(5), 1203-1214. https://doi.org/10.1093/cercor/bhr203