Evidence map›Paper›PMID 32745097›Full record

ArticlePLoS biology2020

Cell-substrate adhesion drives Scar/WAVE activation and phosphorylation by a Ste20-family kinase, which controls pseudopod lifetime.

Shashi Prakash Singh, Peter A Thomason, Sergio Lilla, Matthias Schaks, Qing Tang, Bruce L Goode, Laura M Machesky, Klemens Rottner, Robert H Insall

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
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  12. Under-Agarose Chemotaxis and Migration Assays for Dictyostelium.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  13. Article
  14. Article
  15. WAVE complex regulation by force.Nature cell biology · 2021
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  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

9 authors at 3 institutions in 3 countries.

Shashi Prakash SinghCRUK Beatson Institute, Glasgow, United Kingdom.
Peter A ThomasonCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0003-3104-8392
Sergio LillaCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0003-3142-7640
Matthias SchaksZoological Institute, Technische Universität Braunschweig, Braunschweig, Germany & Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.ORCID 0000-0001-6362-7909
Qing TangBrandeis University, Waltham, Massachusetts, United States of America.
Bruce L GoodeBrandeis University, Waltham, Massachusetts, United States of America.ORCID 0000-0002-6443-5893
Laura M MacheskyCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0002-7592-9856
Klemens RottnerZoological Institute, Technische Universität Braunschweig, Braunschweig, Germany & Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.ORCID 0000-0003-4244-4198
Robert H InsallCRUK Beatson Institute, Glasgow, United Kingdom.ORCID 0000-0003-4898-040X
Cancer Research UK Scotland Institute · GBBrandeis University · USHelmholtz Centre for Infection Research · DE

Funding

MECHNISMS REGULATING ACTIN ASSEMBLYR01GM063691 · NIGMS · BRANDEIS UNIVERSITY · PI GOODE, BRUCE L · 2002 to 2019
$7.5M
Molecular and cellular mechanisms regulating actin dynamicsR35GM134895 · NIGMS · BRANDEIS UNIVERSITY · PI Bruce L Goode · 2020 to 2026
$7.3M
Cancer Research UK 24452Cancer Research UK A17196Cancer Research UK A20017NIGMS NIH HHS R01 GM063691NIGMS NIH HHS R35 GM134895
6 · The paper itself

Abstract

The Scar/WAVE complex is the principal catalyst of pseudopod and lamellipod formation. Here we show that Scar/WAVE's proline-rich domain is polyphosphorylated after the complex is activated. Blocking Scar/WAVE activation stops phosphorylation in both Dictyostelium and mammalian cells, implying that phosphorylation modulates pseudopods after they have been formed, rather than controlling whether they are initiated. Unexpectedly, phosphorylation is not promoted by chemotactic signaling but is greatly stimulated by cell:substrate adhesion and diminished when cells deadhere. Phosphorylation-deficient or phosphomimetic Scar/WAVE mutants are both normally functional and rescue the phenotype of knockout cells, demonstrating that phosphorylation is dispensable for activation and actin regulation. However, pseudopods and patches of phosphorylation-deficient Scar/WAVE last substantially longer in mutants, altering the dynamics and size of pseudopods and lamellipods and thus changing migration speed. Scar/WAVE phosphorylation does not require ERK2 in Dictyostelium or mammalian cells. However, the MAPKKK homologue SepA contributes substantially-sepA mutants have less steady-state phosphorylation, which does not increase in response to adhesion. The mutants also behave similarly to cells expressing phosphorylation-deficient Scar, with longer-lived pseudopods and patches of Scar recruitment. We conclude that pseudopod engagement with substratum is more important than extracellular signals at regulating Scar/WAVE's activity and that phosphorylation acts as a pseudopod timer by promoting Scar/WAVE turnover.

Indexed as

AnimalsCell AdhesionCell Line, TumorChemotaxisCRISPR-Cas SystemsDictyosteliumGene EditingGene Expression RegulationMAP Kinase Kinase Kinase 3MelanocytesMiceMitogen-Activated Protein Kinase 1MutationNIH 3T3 CellsPhenotypePhosphorylationMAP Kinase Kinase Kinase 3Mitogen-Activated Protein Kinase 1Protozoan ProteinsSCAR protein, DictyosteliumWiskott-Aldrich Syndrome Protein Family

Identifiers

PMID32745097
PMCPMC7425996
OpenAlexW3046345051

What OpenQuestion 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 OpenQuestion graph.