Evidence map›Paper›PMID 25427558›Full record

ArticleEMBO reports2015

LRRK2 localizes to endosomes and interacts with clathrin-light chains to limit Rac1 activation.

Andrea M A Schreij, Mathilde Chaineau, Wenjing Ruan, Susan Lin, Philip A Barker, Edward A Fon, Peter S McPherson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. LRRK2 and idiopathic Parkinson's disease.Trends in neurosciences · 2022
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Clathrin Light Chains: Not to Be Taken so Lightly.Frontiers in cell and developmental biology · 2021
    Review
  11. Review
  12. Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  13. Article
  14. Review
  15. Review
  16. Progress inFrontiers in neuroscience · 2020
    Review
  17. Review
  18. Review
  19. Review
  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

7 authors at 1 institution in 1 country.

Andrea M A SchreijDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada.
Mathilde ChaineauDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada.
Wenjing RuanDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada.
Susan LinDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada.
Philip A BarkerDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada.
Edward A FonDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada ted.fon@mcgill.ca peter.mcpherson@mcgill.ca.
Peter S McPhersonDepartment of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada ted.fon@mcgill.ca peter.mcpherson@mcgill.ca.
Montreal Neurological Institute and Hospital · CA

Funding

Canadian Institutes of Health Research MOP-13461
6 · The paper itself

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of dominant-inherited Parkinson's disease (PD), and yet we do not fully understand the physiological function(s) of LRRK2. Various components of the clathrin machinery have been recently found mutated in familial forms of PD. Here, we provide molecular insight into the association of LRRK2 with the clathrin machinery. We report that through its GTPase domain, LRRK2 binds directly to clathrin-light chains (CLCs). Using genome-edited HA-LRRK2 cells, we localize LRRK2 to endosomes on the degradative pathway, where it partially co-localizes with CLCs. Knockdown of CLCs and/or LRRK2 enhances the activation of the small GTPase Rac1, leading to alterations in cell morphology, including the disruption of neuronal dendritic spines. In Drosphila, a minimal rough eye phenotype caused by overexpression of Rac1, is dramatically enhanced by loss of function of CLC and LRRK2 homologues, confirming the importance of this pathway in vivo. Our data identify a new pathway in which CLCs function with LRRK2 to control Rac1 activation on endosomes, providing a new link between the clathrin machinery, the cytoskeleton and PD.

Indexed as

AnimalsAnimals, Genetically ModifiedBase SequenceBrainCells, CulturedChlorocebus aethiopsClathrin Light ChainsCOS CellsDrosophila melanogasterDrosophila ProteinsEndosomesEyeGene Knockdown TechniquesHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Molecular Sequence DataClathrin Light ChainsDrosophila ProteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Serine-Threonine Kinasesrac1 GTP-Binding ProteinRAC1 protein, humanclathrinDrosophila melanogasterendosomesParkinson's diseaseRac1

Identifiers

PMID25427558
PMCPMC4304731
OpenAlexW1999025883

What OpenQuestion holds

Textmetadata
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.