ArticleThe Journal of biological chemistry2014
P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH.
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 80 papers.
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Who cites it
80 citing papers in PubMed, 126 citations in OpenAlex.
- IP3R2-mediated inter-organelle calcium signaling suppresses melanosome degradation.PLoS biology · 2026Article
- P2X4 receptor limits adverse cardiac remodeling following ischemia-reperfusion through regulation of autophagy in cardiac fibroblasts.Cell communication and signaling : CCS · 2026Article
- Preformed fibrils of α-synuclein rapidly activate LRRK2 on early endosomes, driving Rab5 phosphorylation and disrupting endolysosomal and synaptic function.NPJ Parkinson's disease · 2026Article
- The P2X4 purinergic receptor controls the autophagy-related release of small extracellular vesicles from mammary cancer cells under hypoxia.Cell communication and signaling : CCS · 2026Article
- P2X4 receptors as the dynamic regulators of auditory sensory cell activity: a potential new mechanism for protecting hearing?Purinergic signalling · 2026Article
- Possible Roles for Purinergic Receptor P2RX4 in Breast and Prostate Cancers.International journal of molecular sciences · 2025Review
- Intracellular CaBiologia futura · 2025Review
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Cell Type-Specific Expression of Purinergic P2X Receptors in the Hypothalamus.International journal of molecular sciences · 2025Review
- Subcellular localization of the P2X4 receptor in sensory hair cells of Wistar rat cochlea.Histochemistry and cell biology · 2025Article
- Temporal mRNA Expression of Purinergic P2 Receptors in the Brain Following Cerebral Ischemia and Reperfusion: Similarities and Distinct Variations Between Rats and Mice.International journal of molecular sciences · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- ATP released from dying cancer cells stimulates P2X4 receptors and mTOR in their neighbors.Purinergic signalling · 2024Article
- Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration.Journal of neuroinflammation · 2023Review
- Transmembrane Protein 175, a Lysosomal Ion Channel Related to Parkinson's Disease.Biomolecules · 2023Review
- Activated P2X receptors can up-regulate the expressions of inflammation-related genes via NF-κB pathway in spotted sea bass (Frontiers in immunology · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
P2X receptors are commonly known as plasma membrane cation channels involved in a wide variety of cell functions. The properties of these channels have been extensively studied on the plasma membrane. However, studies in amoeba suggest that P2X receptors are also present intracellularly and involved in vesicle fusion with the plasma membrane. Recently, it was shown that in addition to plasma membrane expression, mammalian P2X4 was also localized intracellularly in lysosomes. However, it was not clear whether the lysosomal P2X4 receptors function as channels and how they are activated and regulated. In this paper, we show that both P2X4 and its natural ligand, ATP, are enriched in lysosomes of COS1 and HEK293 cells. By directly recording membrane currents from enlarged lysosomal vacuoles, we demonstrated that lysosomal P2X4 formed channels activated by ATP from the luminal side in a pH-dependent manner. While the acidic pH at the luminal side inhibited P2X4 activity, increasing the luminal pH in the presence of ATP caused P2X4 activation. We further showed that, as for the plasma membrane P2X4, the lysosomal P2X4 was potentiated by ivermectin but insensitive to suramin and PPADS, and it permeated the large cation N-methyl-d-glucamine upon activation. Our data suggest that P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH. Together with the reported fusion effect of intracellular P2X in lower organisms, we speculate that the lysosome-localized P2X4 may play specific roles in membrane trafficking of acidic organelles in mammalian cells.
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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.