ArticleCell calcium2014
Differential mechanisms of action of the mucolipin synthetic agonist, ML-SA1, on insect TRPML and mammalian TRPML1.
Article in Cell calcium, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Mutation of TRPML1 Channel and Pathogenesis of Neurodegeneration in Haimeria.Molecular neurobiology · 2024Review
- UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.Stem cell research & therapy · 2024Article
- Modulation of Lysosomal ClCells · 2023Article
- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity.Biochimie · 2022Article
- Identification and Characterization Analysis of Transient Receptor Potential Mucolipin Protein ofInsects · 2021Article
- Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR).Emerging microbes & infections · 2021Article
- Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021Article
- Review
- Quantitative Imaging of BiochemistryACS central science · 2020Review
- Lysosomal CaCold Spring Harbor perspectives in biology · 2020Review
- Trpml controls actomyosin contractility and couples migration to phagocytosis in fly macrophages.The Journal of cell biology · 2020Article
- Lysosomes as a therapeutic target.Nature reviews. Drug discovery · 2019Review
- Sub-nanomolar sensitive GZnP3 reveals TRPML1-mediated neuronal ZnNature communications · 2019Article
- Effects of silica nanoparticles on endolysosome function in primary cultured neuronsCanadian journal of physiology and pharmacology · 2019Article
- Stimulation of TLR3 triggers release of lysosomal ATP in astrocytes and epithelial cells that requires TRPML1 channels.Scientific reports · 2018Article
- mTORC1 controls lysosomal CaScience signaling · 2018Article
- Rab44, a novel large Rab GTPase, negatively regulates osteoclast differentiation by modulating intracellular calcium levels followed by NFATc1 activation.Cellular and molecular life sciences : CMLS · 2018Article
- Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia.Oxidative medicine and cellular longevity · 2018Article
- Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.Nature structural & molecular biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Mucolipin synthetic agonist 1 (ML-SA1) was recently identified to activate mammalian TRPML channels and shown to alleviate lipid accumulation in lysosomes of cellular models of lysosome storage diseases, mucolipidosis type IV (MLIV) and Niemann-Pick's disease type C (NPC). Owning to its potential use in complimenting genetic studies in Drosophila melanogaster to elucidate the cellular and physiological functions of TRPML channels, we examined the effect of ML-SA1 on Drosophila TRPML expressed in HEK293 cells using whole-cell, inside-out, and whole-lysosome electrophysiological recordings. We previously showed that when expressed in HEK293 cells, Drosophila TRPML was localized and functional on both plasma membrane and endolysosome. We show here that in both inside-out patches excised from the plasma membrane and whole-lysosome recordings from enlarged endolysosome vacuoles, ML-SA1 failed to activate TRPML unless exogenous phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] was applied. At 1 μM ML-SA1, the sensitivity of TRPML to PI(3,5)P2 increased approximately by 10-fold and at 10 μM ML-SA1, the deactivation of PI(3,5)P2-evoked TRPML currents was markedly slowed. On the other hand, constitutive activation of TRPML by a mutation that mimics the varitint-waddler (Va) mutation of mouse TRPML3 rendered the insect channel sensitive to activation by ML-SA1 alone. Moreover, different from the insect TRPML, mouse TRPML1 was readily activated by ML-SA1 independent of PI(3,5)P2. Thus, our data reveal that while ML-SA1 acts as a true agonist at mouse TRPML1, it behaves as an allosteric activator of the Drosophila TRPML, showing dependence on and the ability to stabilize open conformation of the insect channels.
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