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

Two-pore channels and TRP mucolipins are ubiquitous endo-lysosomal cation channels of pathophysiological relevance. Both are Ca 2+ -permeable and regulated by phosphoinositides, principally PI(3,5)P 2 . Accumulating evidence has uncovered synergistic channel activation by PI(3,5)P 2 and endogenous metabolites such as the Ca 2+ 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.