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IP<sub>3</sub> Receptors Preferentially Associate with ER-Lysosome Contact Sites and Selectively Deliver Ca<sup>2+</sup> to Lysosomes.


ABSTRACT: Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) allow extracellular stimuli to redistribute Ca2+ from the ER to cytosol or other organelles. We show, using small interfering RNA (siRNA) and vacuolar H+-ATPase (V-ATPase) inhibitors, that lysosomes sequester Ca2+ released by all IP3R subtypes, but not Ca2+ entering cells through store-operated Ca2+ entry (SOCE). A low-affinity Ca2+ sensor targeted to lysosomal membranes reports large, local increases in cytosolic [Ca2+] during IP3-evoked Ca2+ release, but not during SOCE. Most lysosomes associate with endoplasmic reticulum (ER) and dwell at regions populated by IP3R clusters, but IP3Rs

SUBMITTER: Atakpa P 

PROVIDER: S-EPMC6302550 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature