Inorganic polyphosphate modulates TRPM8 channels

Eleonora Zakharian, Baskaran Thyagarajan, Robert J. French, Evgeny Pavlov, Tibor Rohacs

Research output: Contribution to journalArticle

Abstract

Polyphosphate (polyP) is an inorganic polymer built of tens to hundreds of phosphates, linked by high-energy phosphoanhydride bonds. PolyP forms complexes and modulates activities of many proteins including ion channels. Here we investigated the role of polyP in the function of the transient receptor potential melastatin 8 (TRPM8) channel. Using whole-cell patch-clamp and fluorescent calcium measurements we demonstrate that enzymatic breakdown of polyP by exopolyphosphatase (scPPX1) inhibits channel activity in human embryonic kidney and F-11 neuronal cells expressing TRPM8. We demonstrate that the TRPM8 channel protein is associated with polyP. Furthermore, addition of scPPX1 altered the voltage-dependence and blocked the activity of the purified TRPM8 channels reconstituted into planar lipid bilayers, where the activity of the channel was initiated by cold and menthol in the presence of phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2). The biochemical analysis of the TRPM8 protein also uncovered the presence of poly-(R)-3-hydroxybutyrate (PHB), which is frequently associated with polyP. We conclude that the TRPM8 protein forms a stable complex with polyP and its presence is essential for normal channel activity. Copyright:

Original languageEnglish (US)
Article numbere5404
JournalPLoS One
Volume4
Issue number4
DOIs
StatePublished - Apr 30 2009

Fingerprint

Polyphosphates
polyphosphates
receptors
Phosphatidylinositol 4,5-Diphosphate
Proteins
proteins
3-hydroxybutyric acid
Menthol
Inorganic polymers
menthol
lipid bilayers
Lipid bilayers
3-Hydroxybutyric Acid
phosphatidylinositols
Clamping devices
ion channels
Lipid Bilayers
Polyps
Ion Channels
Human Activities

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Zakharian, E., Thyagarajan, B., French, R. J., Pavlov, E., & Rohacs, T. (2009). Inorganic polyphosphate modulates TRPM8 channels. PLoS One, 4(4), [e5404]. https://doi.org/10.1371/journal.pone.0005404

Inorganic polyphosphate modulates TRPM8 channels. / Zakharian, Eleonora; Thyagarajan, Baskaran; French, Robert J.; Pavlov, Evgeny; Rohacs, Tibor.

In: PLoS One, Vol. 4, No. 4, e5404, 30.04.2009.

Research output: Contribution to journalArticle

Zakharian, E, Thyagarajan, B, French, RJ, Pavlov, E & Rohacs, T 2009, 'Inorganic polyphosphate modulates TRPM8 channels', PLoS One, vol. 4, no. 4, e5404. https://doi.org/10.1371/journal.pone.0005404
Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T. Inorganic polyphosphate modulates TRPM8 channels. PLoS One. 2009 Apr 30;4(4). e5404. https://doi.org/10.1371/journal.pone.0005404
Zakharian, Eleonora ; Thyagarajan, Baskaran ; French, Robert J. ; Pavlov, Evgeny ; Rohacs, Tibor. / Inorganic polyphosphate modulates TRPM8 channels. In: PLoS One. 2009 ; Vol. 4, No. 4.
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