ArticleMolecular biology of the cell2015
TPC2 mediates new mechanisms of platelet dense granule membrane dynamics through regulation of Ca2+ release.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- TPC2 regulates proteomic remodeling, bioenergetic phenotypes, and mitochondrial stress adaptation in melanoma.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Review
- Platelet mitochondria dysfunction in diabetes mellitus: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology.International journal of molecular sciences · 2025Review
- Tetrandrine augments melanoma cell immunogenicity via dual inhibition of autophagic flux and proteasomal activity enhancing MHC-I presentation.Acta pharmacologica Sinica · 2025Article
- OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.The Journal of clinical investigation · 2024Article
- Characterization of Endo-Lysosomal Cation Channels Using Calcium Imaging.Handbook of experimental pharmacology · 2023Article
- Tetrandrine ameliorates cognitive deficits and mitigates tau aggregation in cell and animal models of tauopathies.Journal of biomedical science · 2022Article
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
- Axonal transport of late endosomes and amphisomes is selectively modulated by local CaScience advances · 2022Article
- Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease.Autophagy · 2022Article
- LAMTOR1 inhibition of TRPML1-dependent lysosomal calcium release regulates dendritic lysosome trafficking and hippocampal neuronal function.The EMBO journal · 2022Article
- The ins and outs of virus trafficking through acidic CaCell calcium · 2022Review
- Syntaxin 12 and COMMD3 are new factors that function with VPS33B in the biogenesis of platelet α-granules.Blood · 2022Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- A zinc transporter, transmembrane protein 163, is critical for the biogenesis of platelet dense granules.Blood · 2021Article
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect.PLoS genetics · 2021Article
- N-Methyl-D-Aspartate Receptor Hypofunction in Meg-01 Cells Reveals a Role for Intracellular Calcium Homeostasis in Balancing Megakaryocytic-Erythroid Differentiation.Thrombosis and haemostasis · 2020Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Platelet dense granules (PDGs) are acidic calcium stores essential for normal hemostasis. They develop from late endosomal compartments upon receiving PDG-specific proteins through vesicular trafficking, but their maturation process is not well understood. Here we show that two-pore channel 2 (TPC2) is a component of the PDG membrane that regulates PDG luminal pH and the pool of releasable Ca(2+). Using a genetically encoded Ca(2+) biosensor and a pore mutant TPC2, we establish the function of TPC2 in Ca(2+) release from PDGs and the formation of perigranular Ca(2+) nanodomains. For the first time, Ca(2+) spikes around PDGs--or any organelle of the endolysosome family--are visualized in real time and revealed to precisely mark organelle "kiss-and-run" events. Further, the presence of membranous tubules transiently connecting PDGs is revealed and shown to be dramatically enhanced by TPC2 in a mechanism that requires ion flux through TPC2. "Kiss-and-run" events and tubule connections mediate transfer of membrane proteins and luminal content between PDGs. The results show that PDGs use previously unknown mechanisms of membrane dynamics and content exchange that are regulated by TPC2.
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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.