ArticleScientific reports2016
Characterization of Two-Pore Channel 2 by Nuclear Membrane Electrophysiology.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.Pigment cell & melanoma research · 2024Article
- Endo-Lysosomal Two-Pore Channels and Their Protein Partners.Handbook of experimental pharmacology · 2023Review
- Interneuron odyssey: molecular mechanisms of tangential migration.Frontiers in neural circuits · 2023Review
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
- Review
- Activation of endo-lysosomal two-pore channels by NAADP and PI(3,5)PCell calcium · 2022Review
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release.Circulation · 2021Article
- NAADP Receptors.Cold Spring Harbor perspectives in biology · 2019Review
- Mining of Ebola virus entry inhibitors identifies approved drugs as two-pore channel pore blockers.Biochimica et biophysica acta. Molecular cell research · 2019Article
- Characterization of ADP-ribosyl cyclase 1-like (ARC1-like) activity and NAADP signaling during slow muscle cell development in zebrafish embryos.Developmental biology · 2019Article
- Hypoxia-Inducible Factor-1Oxidative medicine and cellular longevity · 2019Article
- Two-pore channels and disease.Biochimica et biophysica acta. Molecular cell research · 2018Review
- Article
- Organelle membrane derived patches: reshaping classical methods for new targets.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomal calcium (Ca(2+)) release mediated by NAADP triggers signalling cascades that regulate many cellular processes. The identification of two-pore channel 2 (TPC2) as the NAADP receptor advances our understanding of lysosomal Ca(2+) signalling, yet the lysosome is not amenable to traditional patch-clamp electrophysiology. Previous attempts to record TPC2 single-channel activity put TPC2 outside its native environment, which not reflect TPC2's true physiological properties. To test the feasibility of using nuclear membrane electrophysiology for TPC2 channel characterization, we constructed a stable human TPC2-expressing DT40TKO cell line that lacks endogenous InsP3R and RyR (DT40TKO-hTPC2). Immunostaining revealed hTPC2 expression on the ER and nuclear envelope. Intracellular dialysis of NAADP into Fura-2-loaded DT40TKO-hTPC2 cells elicited cytosolic Ca(2+) transients, suggesting that hTPC2 was functionally active. Using nuclear membrane electrophysiology, we detected a ~220 pS single-channel current activated by NAADP with K(+) as the permeant ion. The detected single-channel recordings displayed a linear current-voltage relationship, were sensitive to Ned-19 inhibition, were biphasically regulated by NAADP concentration, and regulated by PKA phosphorylation. In summary, we developed a cell model for the characterization of the TPC2 channel and the nuclear membrane patch-clamp technique provided an alternative approach to rigorously investigate the electrophysiological properties of TPC2 with minimal manipulation.
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