Signal transduction in astrocytes: Localization and release of inorganic polyphosphate

Glia. 2018 Oct;66(10):2126-2136. doi: 10.1002/glia.23466. Epub 2018 Sep 7.


Inorganic polyphosphate (polyP) is present in every cell and is highly conserved from primeval times. In the mammalian cells, polyP plays multiple roles including control of cell bioenergetics and signal transduction. In the brain, polyP mediates signaling between astrocytes via activation of purinergic receptors, however, the mechanisms of polyP release remain unknown. Here we report identification of polyP-containing vesicles in cortical astrocytes and the main triggers that evoke vesicular polyP release. In cultured astrocytes, polyP was localized predominantly within the intracellular vesicular compartments which express vesicular nucleotide transporter VNUT (putative ATP-containing vesicles), but not within the compartments expressing vesicular glutamate transporter 2 (VGLUT2). The number of lysosomes which contain polyP was dependent on the conditions of astrocytes. Release of polyP from a proportion of lysosomes could be induced by calcium ionophores. In contrast, polyP release from the VNUT-containing vesicles could be triggered by various physiological stimuli, such as pH changes, polyP induced polyP release and other stimuli which increase [Ca2+ ] i . These data suggest that astrocytes release polyP predominantly via exocytosis from the VNUT-containing vesicles. © 2018 Wiley Periodicals, Inc.

Keywords: VNUT; astrocytes; inorganic polyphosphate; lysosomes; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Calcium / metabolism
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Exocytosis / physiology
  • Hydrogen-Ion Concentration
  • Intracellular Space / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / deficiency
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Lysosomes / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism
  • Polyphosphates / metabolism*
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Vesicular Glutamate Transport Protein 2 / metabolism


  • Polyphosphates
  • Vesicular Glutamate Transport Protein 2
  • Adenosine Triphosphate
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Lrrk2 protein, mouse
  • Calcium