Journal
JOURNAL OF CELL SCIENCE
Volume 126, Issue 1, Pages 60-66Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.118836
Keywords
Ca2+; Lysosomes; Endoplasmic reticulum; Membrane contact sites; NAADP
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Funding
- Biotechnology and Biological Sciences Research Council [BB/K000942/1]
- Parkinson's UK [K-1107]
- IMPACT studentship from University College London
- BBSRC [BB/G013721/1, BB/K000942/1] Funding Source: UKRI
- MRC [G0801878, MC_G1000735] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/G013721/1, 1676068] Funding Source: researchfish
- Medical Research Council [G0801878, MC_G1000735] Funding Source: researchfish
- Parkinson"
- s UK [H-1202, K-1107] Funding Source: researchfish
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Accumulating evidence implicates acidic organelles of the endolysosomal system as mobilisable stores of Ca2+ but their relationship to the better-characterised endoplasmic reticulum (ER) Ca2+ store remains unclear. Here we show that rapid osmotic permeabilisation of lysosomes evokes prolonged, spatiotemporally complex Ca2+ signals in primary cultured human fibroblasts. These Ca2+ signals comprised an initial response that correlated with lysosomal disruption and secondary long-lasting spatially heterogeneous Ca2+ oscillations that required ER-localised inositol trisphosphate receptors. Electron microscopy identified extensive membrane contact sites between lysosomes and the ER. Mobilisation of lysosomal Ca2+ stores is thus sufficient to evoke ER-dependent Ca2+ release probably through lysosome-ER membrane contact sites, and akin to the proposed mechanism of action of the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Our data identify functional and physical association of discrete Ca2+ stores important for the genesis of Ca2+ signal complexity.
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