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. image