Evidence map›Paper›PMID 31786060›Full record

ArticleCurrent biology : CB2019

WASP Restricts Active Rac to Maintain Cells' Front-Rear Polarization.

Clelia Amato, Peter A Thomason, Andrew J Davidson, Karthic Swaminathan, Shehab Ismail, Laura M Machesky, Robert H Insall

Open access · hybridAbstract read
In one paragraph

Article in Current biology : CB, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

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  5. iScience · 2023
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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 1 institution in 1 country.

Clelia AmatoCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. Electronic address: clelia.amato@ed.ac.uk.
Peter A ThomasonCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Andrew J DavidsonCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Karthic SwaminathanCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Shehab IsmailCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Laura M MacheskyCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Robert H InsallCRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Cancer Research UK Scotland Institute · GB

Funding

Cancer Research UK 24452Cancer Research UK A15672Cancer Research UK A20017Cancer Research UK A24450
6 · The paper itself

Abstract

Efficient motility requires polarized cells, with pseudopods at the front and a retracting rear. Polarization is maintained by restricting the pseudopod catalyst, active Rac, to the front. Here, we show that the actin nucleation-promoting factor Wiskott-Aldrich syndrome protein (WASP) contributes to maintenance of front-rear polarity by controlling localization and cellular levels of active Rac. Dictyostelium cells lacking WASP inappropriately activate Rac at the rear, which affects their polarity and speed. WASP's Cdc42 and Rac interacting binding ("CRIB") motif has been thought to be essential for its activation. However, we show that the CRIB motif's biological role is unexpectedly complex. WASP CRIB mutants are no longer able to restrict Rac activity to the front, and cannot generate new pseudopods when SCAR/WAVE is absent. Overall levels of Rac activity also increase when WASP is unable to bind to Rac. However, WASP without a functional CRIB domain localizes normally at clathrin pits during endocytosis, and activates Arp2/3 complex. Similarly, chemical inhibition of Rac does not affect WASP localization or activation at sites of endocytosis. Thus, the interaction between small GTPases and WASP is more complex than previously thought-Rac regulates a subset of WASP functions, but WASP reciprocally restricts active Rac through its CRIB motif.

Indexed as

Actin-Related Protein 2-3 ComplexActinsAmino Acid SequenceAnimalsCell MovementCell PolarityClathrinDictyosteliumEndocytosisHumansProtein BindingProtein Interaction Domains and MotifsProto-Oncogene Proteins c-aktPseudopodiaWiskott-Aldrich Syndrome ProteinActin-Related Protein 2-3 ComplexActinsClathrinProto-Oncogene Proteins c-aktWiskott-Aldrich Syndrome Proteinactin cytoskeletonactin polymerizationArp2/3 complexcell polarityCRIB motifsmall GTPasesuropod

Identifiers

PMID31786060
PMCPMC6926487
OpenAlexW2989760391

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.