ArticleThe Journal of biological chemistry2014
Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and plasma membrane.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration.EMBO reports · 2026Article
- TRP Channels from Sensory Coding to Physiology.Metabolites · 2025Review
- DMXL1 promotes recruitment of V1-ATPase to lysosomes upon TRPML1 activation.Nature structural & molecular biology · 2025Article
- Bidirectional Allosteric Coupling between PIPInternational journal of molecular sciences · 2024Article
- Homeostasis of cellular amino acids in Acanthamoeba castellanii exposed to different media under amoeba-bacteria coculture conditions.BMC microbiology · 2023Article
- A plant virus hijacks phosphatidylinositol-3,5-bisphosphate to escape autophagic degradation in its insect vector.Autophagy · 2023Article
- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Article
- S-acylation of Orai1 regulates store-operated Ca2+ entry.Journal of cell science · 2022Article
- Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity.Biochimie · 2022Article
- The contribution of ion channels to shaping macrophage behaviour.Frontiers in pharmacology · 2022Review
- TheFrontiers in cell and developmental biology · 2022Article
- Identification and Characterization Analysis of Transient Receptor Potential Mucolipin Protein ofInsects · 2021Article
- Regulation of longevity by depolarization-induced activation of PLC-β-IPProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mechanisms of proton inhibition and sensitization of the cation channel TRPV3.The Journal of general physiology · 2021Article
- Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021Article
- Vascular Dysfunction in Diabetes and Obesity: Focus on TRP Channels.Frontiers in physiology · 2021Review
- TrpML-mediated astrocyte microdomain CaeLife · 2020Article
- Voltage-dependent modulation of TRPA1 currents by diphenhydramine.Cell calcium · 2020Article
- Lysosomal CaCold Spring Harbor perspectives in biology · 2020Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Transient Receptor Potential mucolipin (TRPML) channels are implicated in endolysosomal trafficking, lysosomal Ca(2+) and Fe(2+) release, lysosomal biogenesis, and autophagy. Mutations in human TRPML1 cause the lysosome storage disease, mucolipidosis type IV (MLIV). Unlike vertebrates, which express three TRPML genes, TRPML1-3, the Drosophila genome encodes a single trpml gene. Although the trpml-deficient flies exhibit cellular defects similar to those in mammalian TRPML1 mutants, the biophysical properties of Drosophila TRPML channel remained uncharacterized. Here, we show that transgenic expression of human TRPML1 in the neurons of Drosophila trpml mutants partially suppressed the pupal lethality phenotype. When expressed in HEK293 cells, Drosophila TRPML was localized in both endolysosomes and plasma membrane and was activated by phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) applied to the cytoplasmic side in whole lysosomes and inside-out patches excised from plasma membrane. The PI(3,5)P2-evoked currents were blocked by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but not other phosphoinositides. Using TRPML A487P, which mimics the varitint-waddler (Va) mutant of mouse TRPML3 with constitutive whole-cell currents, we show that TRPML is biphasically regulated by extracytosolic pH, with an optimal pH about 0.6 pH unit higher than that of human TRPML1. In addition to monovalent cations, TRPML exhibits high permeability to Ca(2+), Mn(2+), and Fe(2+), but not Fe(3+). The TRPML currents were inhibited by trivalent cations Fe(3+), La(3+), and Gd(3+). These features resemble more closely to mammalian TRPML1 than TRPML2 and TRPML3, but with some obvious differences. Together, our data support the use of Drosophila for assessing functional significance of TRPML1 in cell physiology.
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