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10.7554/eLife.15887

http://scihub22266oqcxt.onion/10.7554/eLife.15887
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C4909396!4909396!27213518
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suck abstract from ncbi


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pmid27213518      eLife 2016 ; 5 (ä): ä
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  • The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes #MMPMID27213518
  • Garrity AG; Wang W; Collier CM; Levey SA; Gao Q; Xu H
  • eLife 2016[]; 5 (ä): ä PMID27213518show ga
  • Impaired homeostasis of lysosomal Ca2+ causes lysosome dysfunction and lysosomal storage diseases (LSDs), but the mechanisms by which lysosomes acquire and refill Ca2+ are not known. We developed a physiological assay to monitor lysosomal Ca2+ store refilling using specific activators of lysosomal Ca2+ channels to repeatedly induce lysosomal Ca2+ release. In contrast to the prevailing view that lysosomal acidification drives Ca2+ into the lysosome, inhibiting the V-ATPase H+ pump did not prevent Ca2+ refilling. Instead, pharmacological depletion or chelation of Endoplasmic Reticulum (ER) Ca2+ prevented lysosomal Ca2+ stores from refilling. More specifically, antagonists of ER IP3 receptors (IP3Rs) rapidly and completely blocked Ca2+ refilling of lysosomes, but not in cells lacking IP3Rs. Furthermore, reducing ER Ca2+ or blocking IP3Rs caused a dramatic LSD-like lysosome storage phenotype. By closely apposing each other, the ER may serve as a direct and primary source of Ca2+for the lysosome.DOI:http://dx.doi.org/10.7554/eLife.15887.001
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