Evidence map›Paper›PMID 39116126›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex.

Qian Guo, Kai-En Chen, Manuel Gimenez-Andres, Adam P Jellett, Ya Gao, Boris Simonetti, Meihan Liu, Chris M Danson, Kate J Heesom, Peter J Cullen and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. 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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Identification of a VPS29 isoform with restricted association to Retriever and Retromer accessory proteins through autoinhibition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.Molecular medicine (Cambridge, Mass.) · 2025
    Article
  11. Review
  12. Article
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Qian Guo *The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia.
Kai-En Chen *The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia.ORCID 0000-0003-1106-1629
Manuel Gimenez-Andres *School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.ORCID 0000-0002-4100-306X
Adam P JellettSchool of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Ya GaoThe University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia.ORCID 0000-0001-9327-5051
Boris SimonettiSchool of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.ORCID 0000-0002-0304-6640
Meihan LiuThe University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia.ORCID 0009-0006-7463-4497
Chris M DansonSchool of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Kate J HeesomBristol Proteomics Facility, School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.ORCID 0000-0002-5418-5392
Peter J CullenSchool of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.ORCID 0000-0002-9070-8349
Brett M CollinsThe University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia.ORCID 0000-0002-6070-3774

Funding

DHAC | National Health and Medical Research Council (NHMRC) APP1156493DHAC | National Health and Medical Research Council (NHMRC) APP2016410Royal Society (The Royal Society) RSRP/R1/211004UKRI | Medical Research Council (MRC) MR/L007363/1UKRI | Medical Research Council (MRC) MR/P018807/1Wellcome TrustWellcome Trust (WT) 104568/Z/14/ZWellcome Trust (WT) 220260/Z/20/Z
6 · The paper itself

Abstract

Endosomal membrane trafficking is mediated by specific protein coats and formation of actin-rich membrane domains. The Retromer complex coordinates with sorting nexin (SNX) cargo adaptors including SNX27, and the SNX27-Retromer assembly interacts with the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex which nucleates actin filaments establishing the endosomal recycling domain. Crystal structures, modeling, biochemical, and cellular validation reveal how the FAM21 subunit of WASH interacts with both Retromer and SNX27. FAM21 binds the FERM domain of SNX27 using acidic-Asp-Leu-Phe (aDLF) motifs similar to those found in the SNX1 and SNX2 subunits of the ESCPE-1 complex. Overlapping FAM21 repeats and a specific Pro-Leu containing motif bind three distinct sites on Retromer involving both the VPS35 and VPS29 subunits. Mutation of the major VPS35-binding site does not prevent cargo recycling; however, it partially reduces endosomal WASH association indicating that a network of redundant interactions promote endosomal activity of the WASH complex. These studies establish the molecular basis for how SNX27-Retromer is coupled to the WASH complex via overlapping and multiplexed motif-based interactions required for the dynamic assembly of endosomal membrane recycling domains.

Indexed as

EndosomesSorting NexinsVesicular Transport ProteinsBinding SitesCrystallography, X-RayHumansMicrofilament ProteinsModels, MolecularProtein BindingMicrofilament ProteinsSNX27 protein, humanSorting NexinsVesicular Transport ProteinsWASH protein, humanAlphaFoldendosomeFAM21RetromerSNX27

Identifiers

PMID39116126
PMCPMC11331091

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.