Evidence map›Paper›PMID 24752675›Full record

ArticlePloS one2014

LAMTOR2-mediated modulation of NGF/MAPK activation kinetics during differentiation of PC12 cells.

Bettina Thauerer, Paul Voegele, Natascha Hermann-Kleiter, Nikolaus Thuille, Mariana E G de Araujo, Martin Offterdinger, Gottfried Baier, Lukas A Huber, Gabriele Baier-Bitterlich

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Bettina ThauererDivision of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Paul VoegeleDivision of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, Innsbruck, Austria; Division of Cell Genetics, Department for Pharmacology and Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Natascha Hermann-KleiterDivision of Cell Genetics, Department for Pharmacology and Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Nikolaus ThuilleDivision of Cell Genetics, Department for Pharmacology and Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Mariana E G de AraujoDivision of Cell Biology, CCB-Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Martin OffterdingerDivision of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Gottfried BaierDivision of Cell Genetics, Department for Pharmacology and Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Lukas A HuberDivision of Cell Biology, CCB-Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Gabriele Baier-BitterlichDivision of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Innsbruck Medical University · ATUniversität Innsbruck · AT

Funding

Austrian Science Fund FWF P 25044
6 · The paper itself

Abstract

LAMTOR2 (p14), a part of the larger LAMTOR/Ragulator complex, plays a crucial role in EGF-dependent activation of p42/44 mitogen-activated protein kinases (MAPK, ERK1/2). In this study, we investigated the role of LAMTOR2 in nerve growth factor (NGF)-mediated neuronal differentiation. Stimulation of PC12 (rat adrenal pheochromocytoma) cells with NGF is known to activate the MAPK. Pharmacological inhibition of MEK1 as well as siRNA-mediated knockdown of both p42 and p44 MAPK resulted in inhibition of neurite outgrowth. Contrary to expectations, siRNA-mediated knockdown of LAMTOR2 effectively augmented neurite formation and neurite length of PC12 cells. Ectopic expression of a siRNA-resistant LAMTOR2 ortholog reversed this phenotype back to wildtype levels, ruling out nonspecific off-target effects of this LAMTOR2 siRNA approach. Mechanistically, LAMTOR2 siRNA treatment significantly enhanced NGF-dependent MAPK activity, and this effect again was reversed upon expression of the siRNA-resistant LAMTOR2 ortholog. Studies of intracellular trafficking of the NGF receptor TrkA revealed a rapid colocalization with early endosomes, which was modulated by LAMTOR2 siRNA. Inhibition of LAMTOR2 and concomitant destabilization of the remaining members of the LAMTOR complex apparently leads to a faster release of the TrkA/MAPK signaling module and nuclear increase of activated MAPK. These results suggest a modulatory role of the MEK1 adapter protein LAMTOR2 in NGF-mediated MAPK activation required for induction of neurite outgrowth in PC12 cells.

Indexed as

AnimalsCell DifferentiationEndosomesKineticsMAP Kinase Kinase 1Mitogen-Activated Protein KinasesNerve Growth FactorPC12 CellsProteinsRatsReverse Transcriptase Polymerase Chain ReactionLAMTOR2 protein, mouseMAP Kinase Kinase 1Mitogen-Activated Protein KinasesNerve Growth FactorProteins

Identifiers

PMID24752675
PMCPMC3994133
OpenAlexW2057884620

What OpenQuestion holds

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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.