Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals

Sandip Patel, Jonathan S. Marchant, Eugen Brailoiu

Research output: Contribution to journalReview article

66 Scopus citations

Abstract

NAADP is a potent regulator of cytosolic calcium levels. Much evidence suggests that NAADP activates a novel channel located on an acidic (lysosomal-like) calcium store, the mobilisation of which results in further calcium release from the endoplasmic reticulum. Here, we discuss the recent identification of a family of poorly characterized ion channels (the two-pore channels) as endo-lysosomal NAADP receptors. The generation of calcium signals by these channels is likened to those evoked by depolarisation during excitation-contraction coupling in muscle. We discuss the idea that two-pore channels can mediate a trigger release of calcium which is then amplified by calcium-induced calcium release from the endoplasmic reticulum. This is similar to the activation of voltage-sensitive calcium channels and subsequent mobilisation of sarcoplasmic reticulum calcium stores in cardiac tissue. We suggest that two-pore channels may physically interact with ryanodine receptors to account for more direct release of calcium from the endoplasmic reticulum in analogy with the conformational coupling of voltage-sensitive calcium channels and ryanodine receptors in skeletal muscle. Interaction of two-pore channels with other calcium release channels likely occurs between stores " trans-chatter" and possibly within the same store " cis-chatter" We also speculate that trafficking of two-pore channels through the endo-lysosomal system facilitates interactions with calcium entry channels. Strategic placing of two-pore channels thus provides a versatile means of generating spatiotemporally complex cellular calcium signals.

Original languageEnglish (US)
Pages (from-to)480-490
Number of pages11
JournalCell Calcium
Volume47
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Calcium
  • Calcium stores
  • Endosome
  • Lysosome
  • NAADP
  • Two-pore channels

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