Lysosomal agents inhibit store-operated Ca2+ entry
| Autor: | Morgan, Anthony J., Galione, Antony |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
Orai1 ORAI1 Protein Nigericin Ionophore Biology Endoplasmic Reticulum 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lysosome medicine Stromal Interaction Molecule 1 030304 developmental biology Dynamin 0303 health sciences LMP ORAI1 Endoplasmic reticulum Membrane Proteins Bafilomycin STIM1 Cell Biology Cell biology Ca2+ medicine.anatomical_structure chemistry Stim1 GPN Calcium Lysosomes 030217 neurology & neurosurgery Research Article |
| Zdroj: | Journal of Cell Science article-version (VoR) Version of Record |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Pharmacological manipulation of lysosome membrane integrity or ionic movements is a key strategy for probing lysosomal involvement in cellular processes. However, we have found an unexpected inhibition of store-operated Ca2+ entry (SOCE) by these agents. Dipeptides [glycyl-L-phenylalanine 2-naphthylamide (GPN) and L-leucyl-L-leucine methyl ester] that are inducers of lysosomal membrane permeabilization (LMP) uncoupled endoplasmic reticulum Ca2+-store depletion from SOCE by interfering with Stim1 oligomerization and/or Stim1 activation of Orai. Similarly, the K+/H+ ionophore, nigericin, that rapidly elevates lysosomal pH, also inhibited SOCE in a Stim1-dependent manner. In contrast, other strategies for manipulating lysosomes (bafilomycin A1, lysosomal re-positioning) had no effect upon SOCE. Finally, the effects of GPN on SOCE and Stim1 was reversed by a dynamin inhibitor, dynasore. Our data show that lysosomal agents not only release Ca2+ from stores but also uncouple this release from the normal recruitment of Ca2+ influx. Summary: Lysosomal agents uncouple ER Ca2+-release from store-operated Ca2+ entry, predominantly by inhibiting Stim1 oligomerization and its activation of Orai. |
| Databáze: | OpenAIRE |
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