Evidence map›Paper›PMID 37010469›Full record

ArticleThe Journal of cell biology2023

ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution.

Jing Ze Wu, Mariia Zeziulia, Whijin Kwon, Thomas J Jentsch, Sergio Grinstein, Spencer A Freeman

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Review
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  7. LYVAC/PDZD8 is a lysosomal vacuolator.Science (New York, N.Y.) · 2025
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Distinct ClC-6 and ClC-7 ClThe Journal of physiology · 2023
    Article
  18. Distinct ClC-6 and ClC-7 ClThe Journal of physiology · 2023
    Article
  19. Unveiling the impact of lysosomal ion channels: balancing ion signaling and disease pathogenesis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Jing Ze WuProgram in Cell Biology, Hospital for Sick Children , Toronto, Canada.ORCID 0000-0001-6592-320X
Mariia ZeziuliaLeibniz-Forschungsinstitut für Molekulare Pharmakologie and Max-Delbrück-Centrum für Molekulare Medizin , Berlin, Germany.ORCID 0000-0002-5507-0394
Whijin KwonProgram in Cell Biology, Hospital for Sick Children , Toronto, Canada.ORCID 0009-0000-3536-6342
Thomas J JentschLeibniz-Forschungsinstitut für Molekulare Pharmakologie and Max-Delbrück-Centrum für Molekulare Medizin , Berlin, Germany.ORCID 0000-0002-3509-2553
Sergio GrinsteinProgram in Cell Biology, Hospital for Sick Children , Toronto, Canada.ORCID 0000-0002-0795-4160
Spencer A FreemanProgram in Cell Biology, Hospital for Sick Children , Toronto, Canada.ORCID 0000-0003-3455-3714
University of Toronto · CALeibniz-Forschungsinstitut für Molekulare Pharmakologie · DEHospital for Sick Children · CA

Funding

CIHR PJT-169180
6 · The paper itself

Abstract

Degradative organelles contain enzymes that function optimally at the acidic pH generated by the V-ATPase. The resulting transmembrane H+ gradient also energizes the secondary transport of several solutes, including Cl-. We report that Cl- influx, driven by the 2Cl-/H+ exchanger ClC-7, is necessary for the resolution of phagolysosomes formed by macrophages. Cl- transported via ClC-7 had been proposed to provide the counterions required for electrogenic H+ pumping. However, we found that deletion of ClC-7 had a negligible effect on phagosomal acidification. Instead, luminal Cl- was found to be required for activation of a wide range of phagosomal hydrolases including proteases, nucleases, and glycosidases. These findings argue that the primary role of ClC-7 is the accumulation of (phago)lysosomal Cl- and that the V-ATPases not only optimize the activity of degradative hydrolases by lowering the pH but, importantly, also play an indirect role in their activation by providing the driving force for accumulation of luminal Cl- that stimulates hydrolase activity allosterically.

Indexed as

Chloride ChannelsChloridesLysosomesPhagosomesHydrogen-Ion ConcentrationHydrolasesVacuolar Proton-Translocating ATPasesChloride ChannelsChloridesHydrolasesVacuolar Proton-Translocating ATPases

Identifiers

PMID37010469
PMCPMC10072274
OpenAlexW4362520935

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
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 Socratic graph.