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Acidic organelles act as intracellular Ca2+ stores; they actively sequester Ca2+ in their lumina and release it to the cytosol upon activation of endo-lysosomal Ca2+ channels. Recent data suggest important roles of endo-lysosomal Ca2+ channels, the Two-Pore Channels (TPCs) and the TRPML channels (mucolipins), in different aspects of immune-cell function, particularly impacting membrane trafficking, vesicle fusion/fission and secretion. Remarkably, different channels on the same acidic vesicles can couple to different downstream physiology. Endo-lysosomal Ca2+ stores can act under different modalities, be they acting alone (via local Ca2+ nanodomains around TPCs/TRPMLs) or in conjunction with the ER Ca2+ store (to either promote or suppress global ER Ca2+ release). These different modalities impinge upon functions as broad as phagocytosis, cell-killing, anaphylaxis, immune memory, thrombostasis, and chemotaxis.

Original publication

DOI

10.1016/j.ceca.2021.102516

Type

Journal article

Journal

Cell Calcium

Publication Date

01/2022

Volume

101

Keywords

Calcium, TPC, TRPML, endosomes, immune, lysosomes