Evidence map›Paper›PMID 19564905›Full record

ArticlePLoS biology2009

Eps8 regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF).

Elisabetta Menna, Andrea Disanza, Cinzia Cagnoli, Ursula Schenk, Giuliana Gelsomino, Emanuela Frittoli, Maud Hertzog, Nina Offenhauser, Corinna Sawallisch, Hans-Jürgen Kreienkamp and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 137 citations in OpenAlex.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 3 countries.

Elisabetta MennaDepartment of Medical Pharmacology, National Research Council Institute of Neuroscience, University of Milan, Milan, Italy.
Andrea Disanza
Cinzia Cagnoli
Ursula Schenk
Giuliana Gelsomino
Emanuela Frittoli
Maud Hertzog
Nina Offenhauser
Corinna Sawallisch
Hans-Jürgen Kreienkamp
Frank B Gertler
Pier Paolo Di Fiore
Giorgio Scita
Michela Matteoli
FIRC Institute of Molecular Oncology · ITUniversity of Milan · ITNational Research Council · ITUniversität Hamburg · DEFondazione Filarete · ITMassachusetts Institute of Technology · US

Funding

Cytoskeletal Regulation During Growth Cone Migration and Axon GuidanceR01GM068678 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GERTLER, FRANK B · 2003 to 2012
$2.6M
NIGMS NIH HHS GM068678NIGMS NIH HHS R01 GM068678
6 · The paper itself

Abstract

The regulation of filopodia plays a crucial role during neuronal development and synaptogenesis. Axonal filopodia, which are known to originate presynaptic specializations, are regulated in response to neurotrophic factors. The structural components of filopodia are actin filaments, whose dynamics and organization are controlled by ensembles of actin-binding proteins. How neurotrophic factors regulate these latter proteins remains, however, poorly defined. Here, using a combination of mouse genetic, biochemical, and cell biological assays, we show that genetic removal of Eps8, an actin-binding and regulatory protein enriched in the growth cones and developing processes of neurons, significantly augments the number and density of vasodilator-stimulated phosphoprotein (VASP)-dependent axonal filopodia. The reintroduction of Eps8 wild type (WT), but not an Eps8 capping-defective mutant, into primary hippocampal neurons restored axonal filopodia to WT levels. We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation.

Indexed as

ActinsAdaptor Proteins, Signal TransducingAnimalsAxonsBrain-Derived Neurotrophic FactorCell LineCells, CulturedCytoskeletal ProteinsFemaleGreen Fluorescent ProteinsHippocampusHumansMaleMiceMice, Inbred C57BLMice, KnockoutActinsAdaptor Proteins, Signal TransducingBrain-Derived Neurotrophic FactorCytoskeletal ProteinsEps8 protein, mouseGreen Fluorescent ProteinsMitogen-Activated Protein Kinases

Identifiers

PMID19564905
PMCPMC2696597
OpenAlexW2004897775

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.