ArticleThe Journal of cell biology2015
Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 134 citations in OpenAlex.
- Aberrant alternative splicing of purinergic receptor P2RX4 prevents sensitivity towards combinatorial treatment in colorectal and pancreatic cancer.The Journal of pathology · 2026Article
- P2X4 receptors as the dynamic regulators of auditory sensory cell activity: a potential new mechanism for protecting hearing?Purinergic signalling · 2026Article
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- Molecular requirements for mammalian crinophagy highlight a key role for CaResearch square · 2025Article
- Lysosomal TMEM165 controls cellular ion homeostasis and survival by mediating lysosomal CaNature communications · 2025Article
- Subcellular localization of the P2X4 receptor in sensory hair cells of Wistar rat cochlea.Histochemistry and cell biology · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 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
- Loss of CLN3 in microglia leads to impaired lipid metabolism and myelin turnover.Communications biology · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Drosophila TMEM63 and mouse TMEM63A are lysosomal mechanosensory ion channels.Nature cell biology · 2024Article
- ATP released from dying cancer cells stimulates P2X4 receptors and mTOR in their neighbors.Purinergic signalling · 2024Article
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.Autophagy · 2023Article
- Therapeutic targeting of P2X4 receptor and mitochondrial metabolism in clear cell renal carcinoma models.Journal of experimental & clinical cancer research : CR · 2023Article
- Microglial P2X4 receptors promote ApoE degradation and contribute to memory deficits in Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2023Article
- Neuronal P2X4 receptor may contribute to peripheral inflammatory pain in rat spinal dorsal horn.Frontiers in molecular neuroscience · 2023Article
- Lysosomal Ion Channels and Lysosome-Organelle Interactions.Handbook of experimental pharmacology · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Intra-endolysosomal Ca(2+) release is required for endolysosomal membrane fusion with intracellular organelles. However, the molecular mechanisms for intra-endolysosomal Ca(2+) release and the downstream Ca(2+) targets involved in the fusion remain elusive. Previously, we demonstrated that endolysosomal P2X4 forms channels activated by luminal adenosine triphosphate in a pH-dependent manner. In this paper, we show that overexpression of P2X4, as well as increasing endolysosomal P2X4 activity by alkalinization of endolysosome lumen, promoted vacuole enlargement in cells and endolysosome fusion in a cell-free assay. These effects were prevented by inhibiting P2X4, expressing a dominant-negative P2X4 mutant, and disrupting the P2X4 gene. We further show that P2X4 and calmodulin (CaM) form a complex at endolysosomal membrane where P2X4 activation recruits CaM to promote fusion and vacuolation in a Ca(2+)-dependent fashion. Moreover, P2X4 activation-triggered fusion and vacuolation were suppressed by inhibiting CaM. Our data thus suggest a new molecular mechanism for endolysosomal membrane fusion involving P2X4-mediated endolysosomal Ca(2+) release and subsequent CaM activation.
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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.