Evidence map›Paper›PMID 24835460›Full record

ArticleCurrent biology : CB2014

Rab4 orchestrates a small GTPase cascade for recruitment of adaptor proteins to early endosomes.

Ryan S D'Souza, Rachel Semus, Emily A Billings, Corey B Meyer, Kathryn Conger, James E Casanova

Open access · bronzeAbstract 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. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

50 citing papers in PubMed, 82 citations in OpenAlex.

  1. Review
  2. ARF GTPases Function at the Golgi.Sub-cellular biochemistry · 2026
    Review
  3. Article
  4. Loss of ARF5 impairs recovery after lysosomal damage.Frontiers in molecular biosciences · 2025
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  5. Review
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  8. Sec7 regulatory domains scaffold autoinhibited and active conformations.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. IST1 regulates select recycling pathways.Traffic (Copenhagen, Denmark) · 2024
    Article
  10. Article
  11. Review
  12. Article
  13. The Arf family GTPases: Regulation of vesicle biogenesis and beyond.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Review
  14. Article
  15. Protein sorting from endosomes to the TGN.Frontiers in cell and developmental biology · 2023
    Review
  16. Host Cell Signatures of the Envelopment Site within Beta-Herpes Virions.International journal of molecular sciences · 2022
    Review
  17. Article
  18. Article
  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

6 authors at 1 institution in 1 country.

Ryan S D'SouzaDepartment of Cell Biology, University of Virginia Health Sciences Centre, P.O. Box 800732, Charlottesville, VA 22908, USA.
Rachel SemusDepartment of Cell Biology, University of Virginia Health Sciences Centre, P.O. Box 800732, Charlottesville, VA 22908, USA.
Emily A BillingsDepartment of Cell Biology, University of Virginia Health Sciences Centre, P.O. Box 800732, Charlottesville, VA 22908, USA.
Corey B MeyerDepartment of Cell Biology, University of Virginia Health Sciences Centre, P.O. Box 800732, Charlottesville, VA 22908, USA.
Kathryn CongerDepartment of Cell Biology, University of Virginia Health Sciences Centre, P.O. Box 800732, Charlottesville, VA 22908, USA.
James E CasanovaDepartment of Cell Biology, University of Virginia Health Sciences Centre, P.O. Box 800732, Charlottesville, VA 22908, USA. Electronic address: jec9e@virginia.edu.
University of Virginia · US

Funding

INFECTIOUS DISEASES TRAINING PROGRAMT32AI007046 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Alison K Criss, William A Petri · 1985 to 2026
$15.3M
TRAINING IN CELL AND MOLECULAR BIOLOGYT32GM008136 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STUKENBERG, P. TODD · 1985 to 2020
$8.5M
The Role of Arf GTPases in Endocytosis and Postendocytic TransportR01GM078585 · NIGMS · UNIVERSITY OF VIRGINIA · PI CASANOVA, JAMES E. · 2007 to 2010
$1.3M
NIAID NIH HHS T32 AI007046NIGMS NIH HHS GM078585NIGMS NIH HHS R01 GM078585NIGMS NIH HHS T32 GM008136
6 · The paper itself

Abstract

backgroundEarly, sorting endosomes are a major crossroad of membrane traffic, at the intersection of the endocytic and exocytic pathways. The sorting of endosomal cargo for delivery to different subcellular destinations is mediated by a number of distinct coat protein complexes, including adaptor protein 1 (AP-1), AP-3, and Golgi-localized, gamma adaptin ear-containing, Arf-binding (GGAs) protein. Ultrastructural studies suggest that these coats assemble onto tubular subdomains of the endosomal membrane, but the mechanisms of coat recruitment and assembly at this site remain poorly understood.

resultsHere we report that the endosomal Rab protein Rab4 orchestrates a GTPase cascade that results in the sequential recruitment of the ADP-ribosylation factor (Arf)-like protein Arl1; the Arf-specific guanine nucleotide exchange factors BIG1 and BIG2; and the class I Arfs, Arf1 and Arf3. Knockdown of Arf1, or inhibition of BIG1 and BIG2 activity with brefeldin A results in the loss of AP-1, AP-3, and GGA-3, but not Arl1, from endosomal membranes and the formation of elongated tubules. In contrast, depletion of Arl1 randomizes the distribution of Rab4 on endosomal membranes, inhibits the formation of tubular subdomains, and blocks recruitment of BIG1 and BIG2, Arfs, and adaptor protein complexes to the endosome.

conclusionsTogether these findings indicate that Arl1 links Rab4-dependent formation of endosomal sorting domains with downstream assembly of adaptor protein complexes that constitute the endosomal sorting machinery.

Indexed as

Signal TransductionADP-Ribosylation FactorsAnimalsChlorocebus aethiopsCOS CellsEndosomesGTP PhosphohydrolasesHumansIntracellular MembranesMembrane Proteinsrab4 GTP-Binding ProteinsADP-ribosylation factor related proteinsADP-Ribosylation FactorsGTP PhosphohydrolasesMembrane Proteinsrab4 GTP-Binding Proteins

Identifiers

PMID24835460
PMCPMC4059052
OpenAlexW2074170048

What OpenQuestion holds

Textmetadata
LicenceTDM
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.