Evidence map›Paper›PMID 21903581›Full record

ArticleThe Journal of biological chemistry2011

Two-pore channels form homo- and heterodimers.

Katja Rietdorf, Tim M Funnell, Margarida Ruas, Jennifer Heinemann, John Parrington, Antony Galione

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019
    Pooled it
  2. Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Review
  5. TPC Functions in the Immune System.Handbook of experimental pharmacology · 2023
    Article
  6. NAADP-Mediated CaHandbook of experimental pharmacology · 2023
    Article
  7. Targeting the two-pore channel 2 in cancer progression and metastasis.Exploration of targeted anti-tumor therapy · 2022
    Review
  8. Article
  9. Article
  10. NAADP Receptors.Cold Spring Harbor perspectives in biology · 2019
    Review
  11. Endolysosomal CaCancers · 2018
    Review
  12. Article
  13. Two-pore channels and disease.Biochimica et biophysica acta. Molecular cell research · 2018
    Review
  14. Article
  15. NAADP-evoked CaCell calcium · 2017
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Katja RietdorfDepartment of Pharmacology, Oxford University, Oxford OX1 3QT, UK.
Tim M Funnell
Margarida Ruas
Jennifer Heinemann
John Parrington
Antony Galione
University of Oxford · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

Two-pore channels (TPCs) have been recently identified as NAADP-regulated Ca(2+) release channels, which are localized on the endolysosomal system. TPCs have a 12-transmembrane domain (TMD) structure and are evolutionary intermediates between the 24-TMD α-subunits of Na(+) or Ca(2+) channels and the transient receptor potential channel superfamily, which have six TMDs in a single subunit and form tetramers with 24 TMDs as active channels. Based on this relationship, it is predicted that TPCs dimerize to form functional channels, but the dimerization of human TPCs has so far not been studied. Using co-immunoprecipitation studies and a mass spectroscopic analysis of the immunocomplex, we show the presence of homo- and heteromeric complexes for human TPC1 and TPC2. Despite their largely distinct localization, we identified a discrete number of endosomes that coexpressed TPC1 and TPC2. Homo- and heteromerization were confirmed by a FRET study, showing that both proteins interacted in a rotational (N- to C-terminal/head-to-tail) symmetry. This is the first report describing the presence of homomultimeric TPC1 channels and the first study showing that TPCs are capable of forming heteromers.

Indexed as

CalciumCalcium ChannelsEndosomesHEK293 CellsHumansNADPProtein MultimerizationProtein Structure, QuaternaryProtein Structure, TertiaryTwo-Pore ChannelsCalciumCalcium ChannelsNAADPNADPTPCN1 protein, humanTPCN2 protein, humanTwo-Pore Channels

Identifiers

PMID21903581
PMCPMC3199452
OpenAlexW2085642554

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.