Evidence map›Paper›PMID 41200767›Full record

ArticleJournal of cell science2025

Ubiquitylation-dependent Rap2 activation regulates lamellipodia dynamics during cell migration.

Andrew Neumann, Revathi Sampath, Emily Mayerhofer, Valeryia Mikalayeva, Vytenis Arvydas Skeberdis, Ieva Sarapinienė, Rytis Prekeris

Abstract read
In one paragraph

Article in Journal of cell science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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.

Andrew NeumannDepartment of Cell and Developmental Biology, School of Medicine , University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Revathi SampathDepartment of Cell and Developmental Biology, School of Medicine , University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Emily MayerhoferDepartment of Cell and Developmental Biology, School of Medicine , University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Valeryia MikalayevaInstitute of Cardiology , Lithuanian University of Health Sciences, Kaunas LT-50162, Lithuania.
Vytenis Arvydas SkeberdisInstitute of Cardiology , Lithuanian University of Health Sciences, Kaunas LT-50162, Lithuania.
Ieva SarapinienėInstitute of Cardiology , Lithuanian University of Health Sciences, Kaunas LT-50162, Lithuania.
Rytis PrekerisDepartment of Cell and Developmental Biology, School of Medicine , University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.ORCID 0000-0003-3393-1963

Funding

Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)T32GM136444 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MICHAEL A MCMURRAY, Rytis Prekeris · 2020 to 2026
$3.7M
The mechanisms regulating actin dynamics and polarized membrane transport during invadopodia formationR01GM122768 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI PREKERIS, RYTIS · 2018 to 2025
$2.6M
NIGMS NIH HHS R01 GM122768NIGMS NIH HHS T32 GM136444NIH HHS R01 GM122768NIH HHS T32 GM136444Research Council of Lithuania S-MIP-22-60University of Colorado
6 · The paper itself

Abstract

Cell migration is a complex process hallmarked by front-to-back cell polarity that is established by the highly dynamic actin cytoskeleton. Branched actin polymerization creates a lamellipodium at the leading edge of the cell, while the contractile acto-myosin cytoskeleton is present at the lagging edge. Rap2, a Ras GTPase family member, has previously been reported to localize to the lamellipodium as a result of ubiquitylation by a Rab40-Cullin5 E3 ubiquitin ligase complex (Rab40/CRL5). However, how Rap2 functions and how ubiquitylation targets Rap2 to the lamellipodium remained unclear. Here, we demonstrate that Rap2 is recruited to retracting lamellipodia ruffles where it inhibits RhoA, likely through interactions with ARHGAP29, and regulates lamellipodia dynamics, thus facilitating cell migration. Furthermore, using a variety of genetic and pharmacological techniques, we show that Rab40/CRL5-dependent ubiquitylation is required for guanine-nucleotide-exchange factor (GEF)-dependent Rap2 activation, a necessary step for Rap2 targeting to the lamellipodium membrane. As such, we demonstrate how this unique ubiquitylation and activation of Rap2 regulates lamellipodia actin dynamics during cell migration.

Indexed as

Cell MovementPseudopodiarap GTP-Binding ProteinsUbiquitinationCell MembraneFocal AdhesionsGTPase-Activating ProteinsHumansMDA-MB-231 CellsrhoA GTP-Binding ProteinARHGAP29 protein, humanGTPase-Activating ProteinsRAP2A protein, humanrap GTP-Binding ProteinsrhoA GTP-Binding ProteinRHOA protein, humanCell migrationRap2Ubiquitylation

Identifiers

PMID41200767
PMCPMC12752515

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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.