Two-pore channel-2 and inositol trisphosphate receptors coordinate Ca²⁺ signals between lysosomes and the endoplasmic reticulum.

ABSTRACT: Lysosomes and the endoplasmic reticulum (ER) are Ca²⁺ stores mobilized by the second messengers NAADP and IP₃, respectively. Here, we establish Ca²⁺ signals between the two sources as fundamental building blocks that couple local release to global changes in Ca²⁺. Cell-wide Ca²⁺ signals evoked by activation of endogenous NAADP-sensitive channels on lysosomes comprise both local and global components and exhibit a major dependence on ER Ca²⁺ despite their lysosomal origin. Knockout of ER IP₃ receptor channels delays these signals, whereas expression of lysosomal TPC2 channels accelerates them. High-resolution Ca²⁺ imaging reveals elementary events upon TPC2 opening and signals coupled to IP₃ r

SUBMITTER: Yuan Y 

PROVIDER: S-EPMC10931537 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature