Evidence map›Paper›PMID 27213518›Full record

ArticleeLife2016

The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes.

Abigail G Garrity, Wuyang Wang, Crystal Md Collier, Sara A Levey, Qiong Gao, Haoxing Xu

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 1 pooled it
22.0field-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

127 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Activation of Lysosomal Retrograde Transport Triggers TPC1-IP3R1 CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. The IPBiochimica et biophysica acta. Molecular basis of disease · 2025
    Article
  17. Lysosomes' fallback strategies: more than just survival or death.Frontiers in cell and developmental biology · 2025
    Review
  18. Article
  19. Article
  20. Review

67 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Abigail G GarrityNeuroscience Program, University of Michigan, Ann Arbor, United States.
Wuyang WangDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States.
Crystal Md CollierDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States.
Sara A LeveyDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States.
Qiong GaoDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States.
Haoxing XuNeuroscience Program, University of Michigan, Ann Arbor, United States.ORCID 0000-0003-3561-4654
University of Michigan · US

Funding

The Mucolipin TRP Ion ChannelsR01NS062792 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, HAOXING · 2009 to 2018
$3.3M
Early Stage Training in the NeurosciencesT32NS076401 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carol Fuzeti Elias, LESLIE S. SATIN · 2011 to 2026
$3.1M
TRP Ca2+ Channels in the SkinR01AR060837 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, HAOXING · 2012 to 2016
$1.7M
Vesicular Ca2+ Channels in Sarcolemma Repair and Muscular DystrophyR21NS091928 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, HAOXING · 2015 to 2016
$414k
NIAMS NIH HHS R01 AR060837NINDS NIH HHS R01 NS062792NINDS NIH HHS R21 NS091928NINDS NIH HHS T32 NS076401
6 · The paper itself

Abstract

Impaired homeostasis of lysosomal Ca(2+) causes lysosome dysfunction and lysosomal storage diseases (LSDs), but the mechanisms by which lysosomes acquire and refill Ca(2+) are not known. We developed a physiological assay to monitor lysosomal Ca(2+) store refilling using specific activators of lysosomal Ca(2+) channels to repeatedly induce lysosomal Ca(2+) release. In contrast to the prevailing view that lysosomal acidification drives Ca(2+) into the lysosome, inhibiting the V-ATPase H(+) pump did not prevent Ca(2+) refilling. Instead, pharmacological depletion or chelation of Endoplasmic Reticulum (ER) Ca(2+) prevented lysosomal Ca(2+) stores from refilling. More specifically, antagonists of ER IP3 receptors (IP3Rs) rapidly and completely blocked Ca(2+) refilling of lysosomes, but not in cells lacking IP3Rs. Furthermore, reducing ER Ca(2+) or blocking IP3Rs caused a dramatic LSD-like lysosome storage phenotype. By closely apposing each other, the ER may serve as a direct and primary source of Ca(2+)for the lysosome.

Indexed as

AnimalsCalciumCell LineEndoplasmic ReticulumHumansInositol 1,4,5-Trisphosphate ReceptorsLysosomesProton-Motive ForceCalciumInositol 1,4,5-Trisphosphate Receptorscalciumcell biologyERlysosomemouseneuroscience

Identifiers

PMID27213518
PMCPMC4909396
OpenAlexW2398458184

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.