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

Sandip Patel, Yu Yuan, Gihan S Gunaratne, Taufiq Rahman, Jonathan S Marchant

Journal: Cell calcium 2022;103():102543

PMID: 35123238

Free Full Text on PubMed Central View on PubMed

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 Ca-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)P. (4) PI(3,5)P activation is direct through a structurally-resolved binding site. (5) TPCs switch their ion selectivity in an agonist-dependent manner.

Address: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT United Kingdom. Electronic address: [email protected].; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT United Kingdom.; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States of America.; Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.

DOI: 10.1016/j.ceca.2022.102543

Link outs

Free resources

Full Text Sources:

Miscellaneous:

https://assays.cancer.gov/CPTAC-651

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-SERPINA1...

Subscription / membership required

Full Text Sources:

MeSH Terms: Calcium, Calcium Channels, Endosomes, Lysosomes, NADP