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-permeable and regulated by phosphoinositides, principally PI(3,5)P. Accumulating evidence has uncovered synergistic channel activation by PI(3,5)P and endogenous metabolites such as the Ca 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.