Evidence map›Paper›PMID 35931706›Full record

ArticleNature communications2022

Afadin couples RAS GTPases to the polarity rheostat Scribble.

Marilyn Goudreault, Valérie Gagné, Chang Hwa Jo, Swati Singh, Ryan C Killoran, Anne-Claude Gingras, Matthew J Smith

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. 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 2 institutions in 1 country.

Marilyn GoudreaultInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Valérie GagnéInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Chang Hwa JoInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.ORCID http://orcid.org/0000-0002-7819-8307
Swati SinghInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Ryan C KilloranInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Anne-Claude GingrasLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.ORCID http://orcid.org/0000-0002-6090-4437
Matthew J SmithInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada. matthew.james.smith@umontreal.ca.ORCID http://orcid.org/0000-0003-2896-9350
Institute for Research in Immunology and Cancer · CAMount Sinai Hospital · CA

Funding

CIHR
6 · The paper itself

Abstract

AFDN/Afadin is required for establishment and maintenance of cell-cell contacts and is a unique effector of RAS GTPases. The biological consequences of RAS complex with AFDN are unknown. We used proximity-based proteomics to generate an interaction map for two isoforms of AFDN, identifying the polarity protein SCRIB/Scribble as the top hit. We reveal that the first PDZ domain of SCRIB and the AFDN FHA domain mediate a direct but non-canonical interaction between these important adhesion and polarity proteins. Further, the dual RA domains of AFDN have broad specificity for RAS and RAP GTPases, and KRAS co-localizes with AFDN and promotes AFDN-SCRIB complex formation. Knockout of AFDN or SCRIB in epithelial cells disrupts MAPK and PI3K activation kinetics and inhibits motility in a growth factor-dependent manner. These data have important implications for understanding why cells with activated RAS have reduced cell contacts and polarity defects and implicate AFDN as a genuine RAS effector.

Indexed as

Cell Polarityras ProteinsMicrofilament ProteinsPDZ DomainsafadinMicrofilament Proteinsras Proteins

Identifiers

PMID35931706
PMCPMC9355967
OpenAlexW4289886692

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.