Evidence map›Paper›PMID 39812709›Full record

ArticleThe Journal of cell biology2025

A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes.

Amanda Bentley-DeSousa, Agnes Roczniak-Ferguson, Shawn M Ferguson

Abstract read
In one paragraph

Article in The Journal of cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
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

39 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026
    Review
  7. Article
  8. The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026
    Article
  9. Review
  10. Elucidating the molecular interplay between LRRK2 and Rab GTPases.bioRxiv : the preprint server for biology · 2026
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025
    Article
  19. 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

3 authors.

Amanda Bentley-DeSousaDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-3667-4029
Agnes Roczniak-FergusonDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0003-0838-2157
Shawn M FergusonDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-3092-7718

Funding

Aligning Science Across Parkinson's disease ASAP-000580Ludwig FoundationMichael J. Fox Foundation for Parkinson's Research
6 · The paper itself

Abstract

Mutations that increase LRRK2 kinase activity have been linked to Parkinson's disease and Crohn's disease. LRRK2 is also activated by lysosome damage. However, the endogenous cellular mechanisms that control LRRK2 kinase activity are not well understood. In this study, we identify signaling through stimulator of interferon genes (STING) as an activator of LRRK2 via the conjugation of ATG8 to single membranes (CASM) pathway. We furthermore establish that multiple chemical stimuli that perturb lysosomal homeostasis also converge on CASM to activate LRRK2. Although CASM results in the lipidation of multiple ATG8 protein family members, we establish that LRRK2 lysosome recruitment and kinase activation are highly dependent on interactions with the GABARAP member of this family. Collectively, these results define a pathway that integrates multiple stimuli at lysosomes to control the kinase activity of LRRK2. Aberrant activation of LRRK2 via this pathway may be of relevance in both Parkinson's and Crohn's diseases.

Indexed as

Adaptor Proteins, Signal TransducingLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LysosomesMembrane ProteinsMicrotubule-Associated ProteinsAnimalsApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyEnzyme ActivationHEK293 CellsHumansMiceSignal TransductionSTING ProteinAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanMembrane ProteinsMicrotubule-Associated ProteinsSTING1 protein, humanSTING Protein

Identifiers

PMID39812709
PMCPMC11734622

What OpenQuestion holds

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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.