Evidence map›Paper›PMID 30768638›Full record

ArticlePloS one2019

Huntingtin associates with the actin cytoskeleton and α-actinin isoforms to influence stimulus dependent morphology changes.

Adelaide Tousley, Maria Iuliano, Elizabeth Weisman, Ellen Sapp, Heather Richardson, Petr Vodicka, Jonathan Alexander, Neil Aronin, Marian DiFiglia, Kimberly B Kegel-Gleason

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

22 citing papers in PubMed, 33 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

10 authors at 2 institutions in 1 country.

Adelaide TousleyLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Maria IulianoLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Elizabeth WeismanLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Ellen SappLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Heather RichardsonLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Petr VodickaLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Jonathan AlexanderLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Neil AroninDepartment of Medicine and Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Marian DiFigliaLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Kimberly B Kegel-GleasonLaboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
Massachusetts General Hospital · USUniversity of Massachusetts Chan Medical School · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

One response of cells to growth factor stimulus involves changes in morphology driven by the actin cytoskeleton and actin associated proteins which regulate functions such as cell adhesion, motility and in neurons, synaptic plasticity. Previous studies suggest that Huntingtin may be involved in regulating morphology however, there has been limited evidence linking endogenous Huntingtin localization or function with cytoplasmic actin in cells. We found that depletion of Huntingtin in human fibroblasts reduced adhesion and altered morphology and these phenotypes were made worse with growth factor stimulation, whereas the presence of the Huntington's Disease mutation inhibited growth factor induced changes in morphology and increased numbers of vinculin-positive focal adhesions. Huntingtin immunoreactivity localized to actin stress fibers, vinculin-positive adhesion contacts and membrane ruffles in fibroblasts. Interactome data from others has shown that Huntingtin can associate with α-actinin isoforms which bind actin filaments. Mapping studies using a cDNA encoding α-actinin-2 showed that it interacts within Huntingtin aa 399-969. Double-label immunofluorescence showed Huntingtin and α-actinin-1 co-localized to stress fibers, membrane ruffles and lamellar protrusions in fibroblasts. Proximity ligation assays confirmed a close molecular interaction between Huntingtin and α-actinin-1 in human fibroblasts and neurons. Huntingtin silencing with siRNA in fibroblasts blocked the recruitment of α-actinin-1 to membrane foci. These studies support the idea that Huntingtin is involved in regulating adhesion and actin dependent functions including those involving α-actinin.

Indexed as

Actin CytoskeletonActininCell AdhesionCell MembraneCells, CulturedFibroblastsHumansHuntingtin ProteinHuntington DiseaseMicroscopy, ConfocalNeuronsPlatelet-Derived Growth FactorProtein IsoformsRNA InterferenceRNA, Small InterferingActininACTN1 protein, humanHTT protein, humanHuntingtin ProteinPlatelet-Derived Growth FactorProtein IsoformsRNA, Small Interfering

Identifiers

PMID30768638
PMCPMC6377189
OpenAlexW2914097005

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.