Evidence map›Paper›PMID 27418313›Full record

ArticleEMBO reports2016

ALS/FTD-associated FUS activates GSK-3β to disrupt the VAPB-PTPIP51 interaction and ER-mitochondria associations.

Radu Stoica, Sébastien Paillusson, Patricia Gomez-Suaga, Jacqueline C Mitchell, Dawn Hw Lau, Emma H Gray, Rosa M Sancho, Gema Vizcay-Barrena, Kurt J De Vos, Christopher E Shaw and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 2 pooled it
13.5field-weighted citation impact, top 1% 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

174 citing papers in PubMed, 2 syntheses or guidelines pooled it, 245 citations in OpenAlex.

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114 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

13 authors at 1 institution in 1 country.

Radu StoicaDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Sébastien PaillussonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Patricia Gomez-SuagaDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Jacqueline C MitchellDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Dawn Hw LauDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Emma H GrayDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Rosa M SanchoDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Gema Vizcay-BarrenaCentre for Ultrastructural Imaging, King's College London, London, UK.
Kurt J De VosDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.ORCID 0000-0003-2161-6309
Christopher E ShawDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Diane P HangerDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Wendy NobleDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Christopher Cj MillerDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK chris.miller@kcl.ac.uk.ORCID 0000-0002-5130-1845
King's College London · GB

Funding

Medical Research Council G0501573Parkinson's UK G-1308Wellcome Trust 078662
6 · The paper itself

Abstract

Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB-PTPIP51 interaction and ER-mitochondria associations. These disruptions are accompanied by perturbation of Ca(2+) uptake by mitochondria following its release from ER stores, which is a physiological read-out of ER-mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS-expressing cells; mitochondrial ATP production is linked to Ca(2+) levels. Finally, we demonstrate that the FUS-induced reductions to ER-mitochondria associations and are linked to activation of glycogen synthase kinase-3β (GSK-3β), a kinase already strongly associated with ALS/FTD.

Indexed as

Adenosine TriphosphateAmyotrophic Lateral SclerosisAnimalsCalciumDisease Models, AnimalEndoplasmic ReticulumEnzyme ActivationFrontotemporal DementiaGene ExpressionGlycogen Synthase Kinase 3 betaHumansMiceMice, TransgenicMitochondriaMitochondrial ProteinsMutationAdenosine TriphosphateCalciumGlycogen Synthase Kinase 3 betaMitochondrial ProteinsProtein Tyrosine PhosphatasesRMDN3 protein, humanRNA-Binding Protein FUSVAPB protein, humanVesicular Transport Proteinsamyotrophic lateral sclerosisfrontotemporal dementiaglycogen synthase kinase‐3βprotein tyrosine phosphatase interacting protein 51vesicle‐associated membrane protein‐associated protein B

Identifiers

PMID27418313
PMCPMC5007559
OpenAlexW2473774898

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.