Evidence map›Paper›PMID 25160634›Full record

ArticleThe Journal of biological chemistry2014

Interactions with actin monomers, actin filaments, and Arp2/3 complex define the roles of WASP family proteins and cortactin in coordinately regulating branched actin networks.

Luke A Helgeson, Julianna G Prendergast, Andrew R Wagner, Max Rodnick-Smith, Brad J Nolen

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.3field-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

37 citing papers in PubMed, 63 citations in OpenAlex.

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  15. Cortactin in Epithelial-Mesenchymal Transition.Frontiers in cell and developmental biology · 2020
    Review
  16. Article
  17. Article
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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

5 authors at 1 institution in 1 country.

Luke A HelgesonFrom the Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403-1229.
Julianna G PrendergastFrom the Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403-1229.
Andrew R WagnerFrom the Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403-1229.
Max Rodnick-SmithFrom the Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403-1229.
Brad J NolenFrom the Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403-1229 bnolen@uoregon.edu.
University of Oregon · US

Funding

MOLECULAR BIOLOGY AND BIOPHYSICST32GM007759 · NIGMS · UNIVERSITY OF OREGON · PI NOLEN, BRADLEY J · 1985 to 2021
$8.5M
Mechanisms of regulation of Arp2/3 complexR01GM092917 · NIGMS · UNIVERSITY OF OREGON · PI NOLEN, BRADLEY J · 2010 to 2018
$2.9M
NICHD R25 Summer Research Program at the University of OregonR25HD070817 · NICHD · UNIVERSITY OF OREGON · PI EISEN, JUDITH S · 2011 to 2021
$1.1M
NICHD NIH HHS R25 HD070817NICHD NIH HHS R25HD070817NIGMS NIH HHS GM007759NIGMS NIH HHS R01 GM092917NIGMS NIH HHS R01-GM092917NIGMS NIH HHS T32 GM007759
6 · The paper itself

Abstract

Arp2/3 complex is an important actin filament nucleator that creates branched actin filament networks required for formation of lamellipodia and endocytic actin structures. Cellular assembly of branched actin networks frequently requires multiple Arp2/3 complex activators, called nucleation promoting factors (NPFs). We recently presented a mechanism by which cortactin, a weak NPF, can displace a more potent NPF, N-WASP, from nascent branch junctions to synergistically accelerate nucleation. The distinct roles of these NPFs in branching nucleation are surprising given their similarities. We biochemically dissected these two classes of NPFs to determine how their Arp2/3 complex and actin interacting segments modulate their influences on branched actin networks. We find that the Arp2/3 complex-interacting N-terminal acidic sequence (NtA) of cortactin has structural features distinct from WASP acidic regions (A) that are required for synergy between the two NPFs. Our mutational analysis shows that differences between NtA and A do not explain the weak intrinsic NPF activity of cortactin, but instead that cortactin is a weak NPF because it cannot recruit actin monomers to Arp2/3 complex. We use TIRF microscopy to show that cortactin bundles branched actin filaments using actin filament binding repeats within a single cortactin molecule, but that N-WASP antagonizes cortactin-mediated bundling. Finally, we demonstrate that multiple WASP family proteins synergistically activate Arp2/3 complex and determine the biochemical requirements in WASP proteins for synergy. Our data indicate that synergy between WASP proteins and cortactin may play a general role in assembling diverse actin-based structures, including lamellipodia, podosomes, and endocytic actin networks.

Indexed as

Actin-Related Protein 2-3 ComplexActinsAmino Acid SequenceAnimalsBinding, CompetitiveCattleCortactinDNA Mutational AnalysisMicroscopy, FluorescenceMolecular Sequence DataMuscle, SkeletalProtein BindingPseudopodiaPyrenesRabbitsSequence Homology, Amino AcidActin-Related Protein 2-3 ComplexActinsCortactinpyrenePyrenesWiskott-Aldrich Syndrome Protein FamilyActinActin BundlingArp2/3 ComplexCortactinMicroscopySingle-molecule BiophysicsWASP Proteins

Identifiers

PMID25160634
PMCPMC4200246
OpenAlexW2051038367

What OpenQuestion holds

Textmetadata
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.