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In recent years, our understanding of the structure, mechanisms and functions of the endo-lysosomal TPC (two-pore channel) family have grown apace. Gated by the second messengers, NAADP and PI(3,5)P2, TPCs are an integral part of fundamental signal-transduction pathways, but their array and plasticity of cation conductances (Na+, Ca2+, H+) allow them to variously signal electrically, osmotically or chemically. Their relative tissue- and organelle-selective distribution, together with agonist-selective ion permeabilities provides a rich palette from which extracellular stimuli can choose. TPCs are emerging as mediators of immunity, cancer, metabolism, viral infectivity and neurodegeneration as this short review attests.

Original publication

DOI

10.1042/BST20220229

Type

Journal article

Journal

Biochem Soc Trans

Publication Date

31/08/2022

Volume

50

Pages

1143 - 1155

Keywords

Ca2+, NAADP, TPC, lysosomes, Calcium, Calcium Channels, Calcium Signaling, Lysosomes, NADP, Signal Transduction