ArticleThe Journal of biological chemistry2012
Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- IP3R2-mediated inter-organelle calcium signaling suppresses melanosome degradation.PLoS biology · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Mutation of TRPML1 Channel and Pathogenesis of Neurodegeneration in Haimeria.Molecular neurobiology · 2024Review
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Expanding the Toolbox: Novel Modulators of Endolysosomal Cation Channels.Handbook of experimental pharmacology · 2023Article
- Functional In Vitro Assessment of VEGFA/NOTCH2 Signaling Pathway and pRB Proteasomal Degradation and the Clinical Relevance of Mucolipin TRPML2 Overexpression in Glioblastoma Patients.International journal of molecular sciences · 2022Article
- TheFrontiers in cell and developmental biology · 2022Article
- Review
- Estradiol analogs attenuate autophagy, cell migration and invasion by direct and selective inhibition of TRPML1, independent of estrogen receptors.Scientific reports · 2021Article
- TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells.Frontiers in immunology · 2020Review
- Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells.eLife · 2018Article
- Article
- Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.Nature structural & molecular biology · 2017Article
- Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression.Oncotarget · 2016Article
- The mucolipin-2 (TRPML2) ion channel: a tissue-specific protein crucial to normal cell function.Pflugers Archiv : European journal of physiology · 2016Review
- The role of TRPMLs in endolysosomal trafficking and function.Cell calcium · 2015Review
- Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and plasma membrane.The Journal of biological chemistry · 2014Article
- New insights into TRP channels: Interaction with pattern recognition receptors.Channels (Austin, Tex.) · 2014Review
- mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state.Cell · 2013Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The transient receptor potential channels TRPML2 and TRPML3 (MCOLN2 and MCOLN3) are nonselective cation channels. They are widely expressed in mammals. However, little is known about their physiological function(s) and activation mechanism(s). TRPML3 can be activated or rather de-inhibited by exposing it first to sodium-free extracellular solution and subsequently to high extracellular sodium. TRPML3 can also be activated by a variety of small chemical compounds identified in a high throughput screen and is inhibited by low pH. Furthermore, it was found that TRPML3 is constitutively active in low or no sodium-containing extracellular solution. This constitutive activity is independent of the intracellular presence of sodium, and whole-cell current densities are similar with pipette solutions containing cesium, potassium, or sodium. Here, we present mutagenesis data generated based on the hypothesis that negatively charged amino acids in the extracellular loops of TRPML3 may interfere with the observed sodium inhibition. We systematically mutated negatively charged amino acids in the first and second extracellular loops and found that mutating Glu-361 in the second loop has a significant impact on the sodium-mediated block of TRPML3. We further demonstrate that the TRPML3-related cation channel TRPML2 is also activated by lowering the extracellular sodium concentration as well as by a subset of small chemical compounds that were previously identified as activators of TRPML3, thus confirming the functional activity of TRPML2 at the plasma membrane and suggesting similar gating mechanisms for both TRPML channels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.