Coordinating activation of endo-lysosomal two-pore channels and TRP mucolipins

Abstract

Two-pore channels and TRP mucolipins are ubiquitous endo-lysosomal cation channels of pathophysiological relevance. Both are Ca²⁺-permeable and regulated by phosphoinositides, principally PI(3,5)P₂. Accumulating evidence has uncovered synergistic channel activation by PI(3,5)P₂ and endogenous metabolites such as the Ca²⁺ mobilizing messenger NAADP, synthetic agonists including approved drugs and physical cues such as voltage and osmotic pressure. Here, we provide an overview of this coordination.

Keywords: NAADP; PI(3,5)P2; TPC1; TPC2; TRPML1; TRPML2; calcium channel; lysosomes.