Activation of endo-lysosomal two-pore channels by NAADP and PI(3,5)P2. Five things to know

Cell Calcium. 2022 May:103:102543. doi: 10.1016/j.ceca.2022.102543. Epub 2022 Jan 25.

Abstract

Two-pore channels are ancient members of the voltage-gated ion channel superfamily that are expressed predominantly on acidic organelles such as endosomes and lysosomes. Here we review recent advances in understanding how TPCs are activated by their ligands and identify five salient features: (1) TPCs are Ca2+-permeable non-selective cation channels gated by NAADP. (2) NAADP activation is indirect through associated NAADP receptors. (3) TPCs are also Na+-selective channels gated by PI(3,5)P2. (4) PI(3,5)P2 activation is direct through a structurally-resolved binding site. (5) TPCs switch their ion selectivity in an agonist-dependent manner.

Keywords: Ca2+; Endosomes; JPT2; LSM12; Lysosomes; TPC1; TPC2:TPC3; TPCN1; TPCN2; TPCN3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium / metabolism*
  • Calcium Channels / classification
  • Calcium Channels / metabolism
  • Calcium Channels / physiology*
  • Endosomes / metabolism*
  • Lysosomes / metabolism*
  • NADP / analogs & derivatives*
  • NADP / metabolism

Substances

  • Calcium Channels
  • NADP
  • NAADP
  • Calcium