Two-pore channels: going with the flows

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)P-2, 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.

Automated summary

In recent years, there has been a significant progress in understanding the structure, mechanisms and functions of the endo-lysosomal TPC family. TPCs play integral roles in fundamental signal-transduction pathways, with their diverse cation conductances allowing them to signal electrically, osmotically or chemically. Their distribution in different tissues and organelles, together with their selective ion permeabilities, make them important mediators in immunity, cancer, metabolism, viral infectivity and neurodegeneration.