ArticleMolecular and cellular biology2014
TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58 citing papers in PubMed, 81 citations in OpenAlex.
- Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Review
- Two-pore channels in MR1-dependent presentation of Mycobacterium tuberculosis infection.PLoS pathogens · 2025Article
- In silico characterization of the gating and selectivity mechanism of the human TPC2 cation channel.The Journal of general physiology · 2025Article
- Article
- Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Antiviral effects and tissue exposure of tetrandrine against SARS-CoV-2 infection and COVID-19.MedComm · 2023Article
- Expanding the Toolbox: Novel Modulators of Endolysosomal Cation Channels.Handbook of experimental pharmacology · 2023Article
- CaAdvances in experimental medicine and biology · 2023Article
- Neuromasts and Olfactory Organs of Zebrafish Larvae Represent Possible Sites of SARS-CoV-2 Pseudovirus Host Cell Entry.Journal of virology · 2022Article
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
- Article
- Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease.Autophagy · 2022Article
- The ins and outs of virus trafficking through acidic CaCell calcium · 2022Review
- Functional significance of ion channels during macropinosome resolution in immune cells.Frontiers in physiology · 2022Review
- Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.Cellular and molecular life sciences : CMLS · 2021Review
- Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles.Nature communications · 2021Article
- TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.Life science alliance · 2021Article
- Review
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9 authors at 2 institutions in 1 country.
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Abstract
Organelle ion homeostasis within the endo-lysosomal system is critical for physiological functions. Two-pore channels (TPCs) are cation channels that reside in endo-lysosomal organelles, and overexpression results in endo-lysosomal trafficking defects. However, the impact of a lack of TPC expression on endo-lysosomal trafficking is unknown. Here, we characterize Tpcn1 expression in two transgenic mouse lines (Tpcn1(XG716) and Tpcn1(T159)) and show expression of a novel evolutionarily conserved Tpcn1B transcript from an alternative promoter, raising important questions regarding the status of Tpcn1 expression in mice recently described to be Tpcn1 knockouts. We show that the transgenic Tpcn1(T159) line lacks expression of both Tpcn1 isoforms in all tissues analyzed. Using mouse embryonic fibroblasts (MEFs) from Tpcn1(-/-) and Tpcn2(-/-) animals, we show that a lack of Tpcn1 or Tpcn2 expression has no significant impact on resting endo-lysosomal pH or morphology. However, differential effects in endo-lysosomal function were observed upon the loss of Tpcn1 or Tpcn2 expression; thus, while Tpcn1(-/-) MEFs have impaired trafficking of cholera toxin from the plasma membrane to the Golgi apparatus, Tpcn2(-/-) MEFs show slower kinetics of ligand-induced platelet-derived growth factor receptor β (PDGFRβ) degradation, which is dependent on trafficking to lysosomes. Our findings indicate that TPC1 and TPC2 have important but distinct roles in the endo-lysosomal pathway.
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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.