Triggering of Ca2+ signals by NAADP-gated two-pore channels: a role for membrane contact sites?

Biochem Soc Trans. 2012 Feb;40(1):153-7. doi: 10.1042/BST20110693.


NAADP (nicotinic acid-adenine dinucleotide phosphate) is a potent Ca2+-mobilizing messenger implicated in many Ca2+-dependent cellular processes. It is highly unusual in that it appears to trigger Ca2+ release from acidic organelles such as lysosomes. These signals are often amplified by archetypal Ca2+ channels located in the endoplasmic reticulum. Recent studies have converged on the TPCs (two-pore channels) which localize to the endolysosomal system as the likely primary targets through which NAADP mediates its effects. 'Chatter' between TPCs and endoplasmic reticulum Ca2+ channels is disrupted when TPCs are directed away from the endolysosomal system. This suggests that intracellular Ca2+ release channels may be closely apposed, possibly at specific membrane contact sites between acidic organelles and the endoplasmic reticulum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / metabolism*
  • Calcium Signaling*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Intracellular Membranes / metabolism*
  • NADP / analogs & derivatives*
  • NADP / metabolism
  • NADP / physiology
  • Ryanodine Receptor Calcium Release Channel / metabolism


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ryanodine Receptor Calcium Release Channel
  • NADP