Evidence map›Paper›PMID 18191199›Full record

ArticleCell calcium2008

Lysosomes co-localize with ryanodine receptor subtype 3 to form a trigger zone for calcium signalling by NAADP in rat pulmonary arterial smooth muscle.

Nicholas P Kinnear, Christopher N Wyatt, Jill H Clark, Peter J Calcraft, Sidney Fleischer, Loice H Jeyakumar, Graeme F Nixon, A Mark Evans

Abstract read
In one paragraph

Article in Cell calcium, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 1% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.

  1. Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024
    Pooled it
  2. Review
  3. CaBiomedicines · 2025
    Review
  4. Review
  5. Review
  6. Article
  7. Lysosomal TRPML1 triggers global CaFrontiers in physiology · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021
    Article
  13. Article
  14. CaCells · 2020
    Review
  15. Review
  16. Article
  17. NAADP Receptors.Cold Spring Harbor perspectives in biology · 2019
    Review
  18. Article
  19. Evidence of functional ryanodine receptors in rat mesenteric collecting lymphatic vessels.American journal of physiology. Heart and circulatory physiology · 2019
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Nicholas P KinnearSchool of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, NR4 7TJ, Norfolk, UK.
Christopher N Wyatt
Jill H Clark
Peter J Calcraft
Sidney Fleischer
Loice H Jeyakumar
Graeme F Nixon
A Mark Evans
University of East Anglia · GBVanderbilt University · USUniversity of Aberdeen · GB

Funding

British Heart Foundation FS/05/050British Heart Foundation PG/03/065British Heart Foundation PG/03/065/15581British Heart Foundation PG/05/128/19884Wellcome Trust 070772
6 · The paper itself

Abstract

In arterial myocytes the Ca(2+) mobilizing messenger NAADP evokes spatially restricted Ca(2+) bursts from a lysosome-related store that are subsequently amplified into global Ca(2+) waves by Ca(2+)-induced Ca(2+)-release from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs). Lysosomes facilitate this process by forming clusters that co-localize with a subpopulation of RyRs on the SR. We determine here whether RyR subtypes 1, 2 or 3 selectively co-localize with lysosomal clusters in pulmonary arterial myocytes using affinity purified specific antibodies. The density of: (1) alphalgP120 labelling, a lysosome-specific protein, in the perinuclear region of the cell (within 1.5mum of the nucleus) was approximately 4-fold greater than in the sub-plasmalemmal (within 1.5mum of the plasma membrane) and approximately 2-fold greater than in the extra-perinuclear (remainder) regions; (2) RyR3 labelling within the perinuclear region was approximately 4- and approximately 14-fold greater than that in the extra-perinuclear and sub-plasmalemmal regions, and approximately 2-fold greater than that for either RyR1 or RyR2; (3) despite there being no difference in the overall densities of fluorescent labelling of lysosomes and RyR subtypes between cells, co-localization with alphalgp120 labelling within the perinuclear region was approximately 2-fold greater for RyR3 than for RyR2 or RyR1; (4) co-localization between alphalgp120 and each RyR subtype declined markedly outside the perinuclear region. Furthermore, selective block of RyR3 and RyR1 with dantrolene (30muM) abolished global Ca(2+) waves but not Ca(2+) bursts in response to intracellular dialysis of NAADP (10nM). We conclude that a subpopulation of lysosomes cluster in the perinuclear region of the cell and form junctions with SR containing a high density of RyR3 to comprise a trigger zone for Ca(2+) signalling by NAADP.

Indexed as

Calcium SignalingAnimalsCalciumCells, CulturedFluorescenceHeartLungLysosomesMaleMuscle, Smooth, VascularNADPProtein IsoformsPulmonary ArteryRatsRats, WistarRyanodineCalciumNAADPNADPProtein IsoformsRyanodineRyanodine Receptor Calcium Release Channel

Identifiers

PMID18191199
PMCPMC3982125
OpenAlexW2048465199

What OpenQuestion holds

Textmetadata
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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.