Evidence map›Paper›PMID 22513087›Full record

ArticleMolecular biology of the cell2012

Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer.

Da Jia, Timothy S Gomez, Daniel D Billadeau, Michael K Rosen

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

130 citing papers in PubMed, 199 citations in OpenAlex.

  1. Article
  2. Review
  3. TheMolecular biology of the cell · 2026
    Article
  4. Article
  5. Article
  6. ThebioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Article
  9. Article
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  11. Article
  12. 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
  13. Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.Molecular medicine (Cambridge, Mass.) · 2025
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

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

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

4 authors at 3 institutions in 1 country.

Da JiaDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Timothy S Gomez
Daniel D Billadeau
Michael K Rosen
Mayo Clinic · USHoward Hughes Medical Institute · USSouthwestern 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
TRAINING PROGRAM IN ALLERGIC DISEASEST32AI007047 · NIAID · MAYO CLINIC ROCHESTER · PI KITA, HIROHITO · 1985 to 2016
$2.0M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI065474NIAID NIH HHS R01-AI065474NIAID NIH HHS T32 AI007047NIAID NIH HHS T32-AI07047NIGMS NIH HHS R01 GM056322NIGMS NIH HHS R01-GM056322
6 · The paper itself

Abstract

Wiskott-Aldrich syndrome protein (WASPs) control actin dynamics in cellular processes, including cell motility, receptor-mediated endocytosis, bacterial invasion, and vesicular trafficking. We demonstrated that WASH, a recently identified WASP family protein, colocalizes on endosomal subdomains with the cargo-selective complex (CSC) of the retromer, where it regulates retrograde sorting from endosomes in an actin-dependent manner. However, the mechanism of WASH recruitment to these retromer-enriched endosomal subdomains is unclear. Here we show that a component of the WASH regulatory complex (SHRC), FAM21, which contains 21 copies of a novel L-F-[D/E](3-10)-L-F motif, directly interacts with the retromer CSC protein VPS35. Endosomal localization of FAM21 is VPS35 dependent and relies on multivalency of FAM21 repeat elements. Using a combination of pull-down assays and isothermal calorimetry, we demonstrate that individual repeats can bind CSC, and binding affinity varies among different FAM21 repeats. A high-affinity repeat can be converted into a low-affinity one by mutation of a hydrophobic residue within the motif. These in vitro data mirror the localization of FAM21 to retromer-coated vesicles in cells. We propose that multivalency enables FAM21 to sense the density of retromer on membranes, allowing coordination of SHRC recruitment, and consequent actin polymerization, with retromer sorting domain organization/maturation.

Indexed as

ActinsAmino Acid MotifsAmino Acid SequenceAnimalsBinding SitesCattleElectrophoresis, Polyacrylamide GelEndosomesHeLa CellsHumansImmunoprecipitationLuminescent ProteinsMicrofilament ProteinsMicroscopy, ConfocalMolecular Sequence DataMutationActinsLuminescent ProteinsMicrofilament ProteinsVesicular Transport ProteinsVPS35 protein, humanWASH protein, human

Identifiers

PMID22513087
PMCPMC3374753
OpenAlexW2032793177

What OpenQuestion 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 OpenQuestion graph.