Evidence map›Paper›PMID 24980502›Full record

ArticleCurrent biology : CB2014

Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation.

Ian J McGough, Florian Steinberg, Da Jia, Peter A Barbuti, Kirsty J McMillan, Kate J Heesom, Alan L Whone, Maeve A Caldwell, Daniel D Billadeau, Michael K Rosen and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Current biology : CB, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
8.5field-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

109 citing papers in PubMed, 217 citations in OpenAlex.

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  13. COVID-19 Alters Inflammatory, Mitochondrial, and Protein Clearance Pathway Genes: Potential Implications for New-onset Parkinsonism in Patients.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  14. Article
  15. Review
  16. Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Retromer-dependent lysosomal stress in Parkinson's disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  18. VPS35 and retromer dysfunction in Parkinson's disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Ian J McGoughThe Henry Wellcome Integrated Signaling Laboratories, School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Florian SteinbergThe Henry Wellcome Integrated Signaling Laboratories, School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Da JiaDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Peter A BarbutiHenry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
Kirsty J McMillanThe Henry Wellcome Integrated Signaling Laboratories, School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Kate J HeesomProteomics Facility, School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Alan L WhoneInstitute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK.
Maeve A CaldwellHenry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
Daniel D BilladeauDepartments of Biochemistry and Molecular Biology and Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Michael K RosenDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Peter J CullenThe Henry Wellcome Integrated Signaling Laboratories, School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK. Electronic address: pete.cullen@bristol.ac.uk.
University of Bristol · GBFrenchay Hospital · GBMayo Clinic in Arizona · USSouthwestern Medical Center · USThe University of Texas Southwestern Medical Center · US

Funding

STRUCTURAL STUDY OF RHO-GTPASE REGULATORS AND EFFECTORSR01GM056322 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI ROSEN, MICHAEL K · 1997 to 2019
$5.7M
Regulation of Actin Dynamics During T Cell ActivationR01AI065474 · NIAID · MAYO CLINIC ROCHESTER · PI BILLADEAU, DANIEL D · 2005 to 2014
$3.1M
Howard Hughes Medical InstituteMedical Research Council MR/K018299/1NIAID NIH HHS R01 AI065474NIGMS NIH HHS R01 GM056322NIGMS NIH HHS R01-GM56322Wellcome TrustWellcome Trust 085743Wellcome Trust 089928
6 · The paper itself

Abstract

Retromer is a protein assembly that plays a central role in orchestrating export of transmembrane-spanning cargo proteins from endosomes into retrieval pathways destined for the Golgi apparatus and the plasma membrane [1]. Recently, a specific mutation in the retromer component VPS35, VPS35(D620N), has linked retromer dysfunction to familial autosomal dominant and sporadic Parkinson disease [2, 3]. However, the effect of this mutation on retromer function remains poorly characterized. Here we established that in cells expressing VPS35(D620N) there is a perturbation in endosome-to-TGN transport but not endosome-to-plasma membrane recycling, which we confirm in patient cells harboring the VPS35(D620N) mutation. Through comparative stable isotope labeling by amino acids in cell culture (SILAC)-based analysis of wild-type VPS35 versus the VPS35(D620N) mutant interactomes, we establish that the major defect of the D620N mutation lies in the association to the actin-nucleating Wiskott-Aldrich syndrome and SCAR homolog (WASH) complex. Moreover, using isothermal calorimetry, we establish that the primary defect of the VPS35(D620N) mutant is a 2.2 ± 0.5-fold decrease in affinity for the WASH complex component FAM21. These data define the primary molecular defect in retromer assembly that arises from the VPS35(D620N) mutation and, by revealing functional effects on retromer-mediated endosome-to-TGN transport, provide new insight into retromer deregulation in Parkinson disease.

Indexed as

Ankyrin RepeatAntigens, NeoplasmBinding SitesCell Line, TumorCells, CulturedEndosomesGolgi ApparatusHeLa CellsHumansIntracellular Signaling Peptides and ProteinsMicrofilament ProteinsMolecular ChaperonesMutationParkinson DiseaseProtein BindingProtein TransportAntigens, NeoplasmDNAJC13 protein, humanENTR1 protein, humanIntracellular Signaling Peptides and ProteinsMicrofilament ProteinsMolecular ChaperonesVesicular Transport ProteinsVPS35 protein, humanWASH protein, human

Identifiers

PMID24980502
PMCPMC4110399
OpenAlexW1973911766

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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.