Evidence map›Paper›PMID 23109420›Full record

ArticleMolecular and cellular biology2013

Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons.

Lukáš Čajánek, Ranjani Sri Ganji, Catarina Henriques-Oliveira, Spyridon Theofilopoulos, Peter Koník, Vítězslav Bryja, Ernest Arenas

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In one paragraph

Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

28 citing papers in PubMed, 48 citations in OpenAlex.

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  17. Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019
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  18. Planar cell polarity geneEMBO reports · 2018
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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 3 institutions in 2 countries.

Lukáš ČajánekMolecular Neurobiology Unit, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Ranjani Sri Ganji
Catarina Henriques-Oliveira
Spyridon Theofilopoulos
Peter Koník
Vítězslav Bryja
Ernest Arenas
Karolinska Institutet · SECzech Academy of Sciences, Institute of Biophysics · CZMasaryk University · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. Finally, using ventral midbrain neurosphere cultures, we demonstrate that the generation of DA neurons in culture is impaired after Tiam1 knockdown, indicating that Tiam1 is required for midbrain DA differentiation. In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCasein Kinase ICell DifferentiationDishevelled ProteinsDopaminergic NeuronsFibroblastsGene Expression Regulation, DevelopmentalGuanine Nucleotide Exchange FactorsHumansImmunoprecipitationMesencephalonMiceNeuropeptidesPhosphoproteinsrac1 GTP-Binding ProteinAdaptor Proteins, Signal TransducingCasein Kinase IDishevelled ProteinsDVL3 protein, humanDvl3 protein, mouseGuanine Nucleotide Exchange FactorsNeuropeptidesPhosphoproteinsrac1 GTP-Binding ProteinRac1 protein, mouserac GTP-Binding ProteinsTIAM1 protein, humanTiam1 protein, mouseT-Lymphoma Invasion and Metastasis-inducing Protein 1Wnt-5a ProteinWnt5a protein, mouseWnt Proteins

Identifiers

PMID23109420
PMCPMC3536309
OpenAlexW2149849592

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.