Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals

作者：Kilpatrick Bethan S; Eden Emily R; Schapira Anthony H; Futter Clare E; Patel Sandip^*

来源：Journal of Cell Science, 2013, 126(1): 60-66.

DOI：10.1242/jcs.118836

• Ca2+
• Lysosomes
• Endoplasmic reticulum
• Membrane contact sites
• NAADP

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.

• 出版日期2013-1-1