Evidence map›Paper›PMID 21613607›Full record

ArticleAmerican journal of physiology. Cell physiology2011

Reconstitution of lysosomal NAADP-TRP-ML1 signaling pathway and its function in TRP-ML1(-/-) cells.

Fan Zhang, Ming Xu, Wei-Qing Han, Pin-Lan Li

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
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

31 citing papers in PubMed, 46 citations in OpenAlex.

  1. Vascular mechanotransduction.Physiological reviews · 2023
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021
    Article
  8. Roles of NADMolecules (Basel, Switzerland) · 2020
    Review
  9. Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases.International journal of molecular sciences · 2020
    Review
  10. Contribution of NAADP to Glutamate-Evoked Changes in CaFrontiers in cell and developmental biology · 2020
    Article
  11. Review
  12. Article
  13. The lysosomal CaThe Journal of biological chemistry · 2017
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Regulation of dynein-mediated autophagosomes trafficking by ASM in CASMCs.Frontiers in bioscience (Landmark edition) · 2016
    Article
  19. Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on Macrophage Viability and Polarization.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2015
    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

4 authors at 1 institution in 1 country.

Fan ZhangDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Ming Xu
Wei-Qing Han
Pin-Lan Li
Virginia Commonwealth University Medical Center · US

Funding

Regulation of Lysosomes in Autophagy in Coronary Arterial MyocytesR01HL057244 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2001 to 2021
$6.7M
Subendothelial Exosomes in Coronary Microvascular DysfunctionR01HL075316 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2004 to 2024
$6.7M
NAADP-Sensitive Lysosomal Ca2+ Release Channels-TRP-ML1 in Arterial MyocytesR01HL091464 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2009 to 2013
$2.2M
MECHANISM OF CORONARY ENDOTHELIUM MEDIATED VASODILATIONR29HL057244 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI LI, PIN-LAN · 1997 to 2000
$101k
NHLBI NIH HHS HL057244-09NHLBI NIH HHS HL075316-0NHLBI NIH HHS R01 HL057244NHLBI NIH HHS R01 HL075316NHLBI NIH HHS R01 HL091464
6 · The paper itself

Abstract

It is well known that the mutation of TRP-ML1 (transient receptor potential-mucolipin-1) causes mucolipidosis IV, a lysosomal storage disease. Given that lysosomal nicotinic acid adenine dinucleotide phosphate (NAADP)-Ca(2+) release channel activity is associated with TRP-ML1, the present study was designed to test the hypothesis that NAADP regulates lysosome function via activation of TRP-ML1 channel activity. Using lysosomal preparations from wild-type (TRP-ML1(+/+)) human fibroblasts, channel reconstitution experiments demonstrated that NAADP (0.01-1.0 μM) produced a concentration-dependent increase in TRP-ML1 channel activity. This NAADP-induced activation of TRP-ML1 channels could not be observed in lysosomes from TRP-ML1(-/-) cells, but was restored by introducing a TRP-ML1 transgene into these cells. Microscopic Ca(2+) fluorescence imaging showed that NAADP significantly increased intracellular Ca(2+) concentration to 302.4 ± 74.28 nM (vs. 180 ± 44.13 nM of the basal) in TRP-ML1(+/+) cells, but it had no effect in TRP-ML1(-/-) cells. If a TRP-ML1 gene was transfected into TRP-ML1(-/-) cells, the Ca(2+) response to NAADP was restored to the level comparable to TRP-ML1(+/+) cells. Functionally, confocal microscopy revealed that NAADP significantly enhanced the dynamic interaction of endosomes and lysosomes and the lipid delivery to lysosomes in TRP-ML1(+/+) cells. This functional action of NAADP was abolished in TRP-ML1(-/-) cells, but restored after TRP-ML1 gene was rescued in these cells. Our results suggest that NAADP increases lysosomal TRP-ML1 channel activity to release Ca(2+), which promotes the interaction of endosomes and lysosomes and thereby regulates lipid transport to lysosomes. Failure of NAADP-TRP-ML1 signaling may be one of the important mechanisms resulting in intracellular lipid trafficking disorder and consequent mucolipidosis.

Indexed as

Calcium SignalingCell LineCeramidesEndocytosisEndosomesFibroblastsHumansLysosomesMembrane PotentialsMicroscopy, ConfocalMicroscopy, FluorescenceNADPRecombinant Fusion ProteinsTime FactorsTransfectionTransient Receptor Potential ChannelsCeramidesMCOLN1 protein, humanNAADPNADPRecombinant Fusion ProteinsTransient Receptor Potential ChannelsTRPM Cation Channels

Identifiers

PMID21613607
PMCPMC3154564
OpenAlexW2129079454

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.