Matches in SemOpenAlex for { <https://semopenalex.org/work/W3011823564> ?p ?o ?g. }
- W3011823564 abstract "Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca2+-signals and non-selective cation currents, the other weaker Ca2+-signals and Na+-selective currents. These properties were mirrored by the Ca2+-mobilizing messenger, NAADP and the phosphoinositide, PI(3,5)P2, respectively. Agonist action was differentially inhibited by mutation of a single TPC2 residue and coupled to opposing changes in lysosomal pH and exocytosis. Our findings resolve conflicting reports on the permeability and gating properties of TPC2 and they establish a new paradigm whereby a single ion channel mediates distinct, functionally-relevant ionic signatures on demand." @default.
- W3011823564 created "2020-03-23" @default.
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- W3011823564 date "2020-03-16" @default.
- W3011823564 modified "2023-10-17" @default.
- W3011823564 title "Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function" @default.
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- W3011823564 doi "https://doi.org/10.7554/elife.54712" @default.
- W3011823564 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7108868" @default.
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