Evidence map›Paper›PMID 21685497›Full record

ArticleThe Journal of biological chemistry2011

Mechanism of actin filament bundling by fascin.

Silvia Jansen, Agnieszka Collins, Changsong Yang, Grzegorz Rebowski, Tatyana Svitkina, Roberto Dominguez

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% 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

108 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.

  1. Pooled it
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  16. Structural insights into full-length human fascin1: a target for cancer treatment.Acta crystallographica. Section F, Structural biology communications · 2025
    Article
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48 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Silvia JansenDepartment of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Agnieszka Collins
Changsong Yang
Grzegorz Rebowski
Tatyana Svitkina
Roberto Dominguez
University of Pennsylvania · US

Funding

Structure-Function of the CytoskeletonP01HL086655 · NHLBI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MORGAN, KATHLEEN G · 2007 to 2011
$8.8M
BAR PROTEINS LINKING MEMBRANE AND CYTOSKELETON DYNAMICSR01MH087950 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI DOMINGUEZ, ROBERTO · 2010 to 2020
$4.0M
MOLECULAR DESIGN OF FILOPODIA, CELL'S SENSORY ORGANELLESR01GM070898 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI SVITKINA, TATYANA · 2004 to 2012
$2.7M
Transmission Electron MicroscopeS10RR022482 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI SVITKINA, TATYANA · 2007 to 2007
$307k
NCRR NIH HHS S10 RR022482NCRR NIH HHS S10 RR-22482NHLBI NIH HHS HL086655NHLBI NIH HHS P01 HL086655NIGMS NIH HHS GM070898NIGMS NIH HHS R01 GM070898NIMH NIH HHS MH087950NIMH NIH HHS R01 MH087950
6 · The paper itself

Abstract

Fascin is the main actin filament bundling protein in filopodia. Because of the important role filopodia play in cell migration, fascin is emerging as a major target for cancer drug discovery. However, an understanding of the mechanism of bundle formation by fascin is critically lacking. Fascin consists of four β-trefoil domains. Here, we show that fascin contains two major actin-binding sites, coinciding with regions of high sequence conservation in β-trefoil domains 1 and 3. The site in β-trefoil-1 is located near the binding site of the fascin inhibitor macroketone and comprises residue Ser-39, whose phosphorylation by protein kinase C down-regulates actin bundling and formation of filopodia. The site in β-trefoil-3 is related by pseudo-2-fold symmetry to that in β-trefoil-1. The two sites are ∼5 nm apart, resulting in a distance between actin filaments in the bundle of ∼8.1 nm. Residue mutations in both sites disrupt bundle formation in vitro as assessed by co-sedimentation with actin and electron microscopy and severely impair formation of filopodia in cells as determined by rescue experiments in fascin-depleted cells. Mutations of other areas of the fascin surface also affect actin bundling and formation of filopodia albeit to a lesser extent, suggesting that, in addition to the two major actin-binding sites, fascin makes secondary contacts with other filaments in the bundle. In a high resolution crystal structure of fascin, molecules of glycerol and polyethylene glycol are bound in pockets located within the two major actin-binding sites. These molecules could guide the rational design of new anticancer fascin inhibitors.

Indexed as

Actin CytoskeletonAnimalsBinding SitesCarrier ProteinsCell Line, TumorCrystallography, X-RayHumansMiceMicrofilament ProteinsMutationPhosphorylationProtein Kinase CProtein Structure, TertiaryPseudopodiaStructure-Activity RelationshipCarrier ProteinsfascinMicrofilament ProteinsProtein Kinase C

Identifiers

PMID21685497
PMCPMC3191048
OpenAlexW2024230071

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.