ArticleDevelopmental cell2013
A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis.
Article in Developmental cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.
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Who cites it
203 citing papers in PubMed, 305 citations in OpenAlex.
- Quantitative comparison of PI(3,5)PMolecular biology of the cell · 2026Article
- TPC1-dependent control of endosomal pH and transferrin uptake determines cellular iron status.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Peroxisome-derived ether lipids regulate lysosomal exocytosis.The EMBO journal · 2026Article
- PIKfyve is required for efficient phagosomal Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes.Journal of cell science · 2026Article
- TRPML1 suppresses pulmonary fibrosis by limiting collagen and elastin deposition.The EMBO journal · 2026Article
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- Extracellular vesicle dysfunction contributes to synaptic and cognitive deficits in a mouse model of Angelman syndrome.Progress in neurobiology · 2026Article
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Macrophages discriminate and sort pathogenic bacteria and apoptotic material during dual-target phagocytosis.PloS one · 2026Article
- Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue.Cell death & disease · 2025Article
- Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages.International journal of molecular sciences · 2025Review
- TRIB3 Links Endoplasmic Reticulum Stress to Impaired Efferocytosis in Atherosclerosis.Circulation research · 2025Article
- Quantitative comparison of PI(3,5)PbioRxiv : the preprint server for biology · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?Bioactive materials · 2025Review
- Inter-Organelle Crosstalk in Oxidative Distress: A Unified TRPM2-NOX2 Mediated Vicious Cycle Involving CaAntioxidants (Basel, Switzerland) · 2025Review
- TRPML2 in distinct states reveals the activation and modulation principles of the TRPML family.Nature communications · 2025Article
- TFEB-mediated proinflammatory response in murine macrophages induced by acute Alpha7 nicotinic receptor activation.Journal of leukocyte biology · 2025Article
- Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- TRPML-1 Dysfunction and Renal Tubulopathy in Mucolipidosis Type IV.Journal of the American Society of Nephrology : JASN · 2025Article
143 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
22 authors at 4 institutions in 1 country.
Funding
Abstract
Phagocytosis of large extracellular particles such as apoptotic bodies requires delivery of the intracellular endosomal and lysosomal membranes to form plasmalemmal pseudopods. Here, we identified mucolipin TRP channel 1 (TRPML1) as the key lysosomal Ca2+ channel regulating focal exocytosis and phagosome biogenesis. Both particle ingestion and lysosomal exocytosis are inhibited by synthetic TRPML1 blockers and are defective in macrophages isolated from TRPML1 knockout mice. Furthermore, TRPML1 overexpression and TRPML1 agonists facilitate both lysosomal exocytosis and particle uptake. Using time-lapse confocal imaging and direct patch clamping of phagosomal membranes, we found that particle binding induces lysosomal PI(3,5)P2 elevation to trigger TRPML1-mediated lysosomal Ca2+ release specifically at the site of uptake, rapidly delivering TRPML1-resident lysosomal membranes to nascent phagosomes via lysosomal exocytosis. Thus phagocytic ingestion of large particles activates a phosphoinositide- and Ca2+-dependent exocytosis pathway to provide membranes necessary for pseudopod extension, leading to clearance of senescent and apoptotic cells in vivo.
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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.