Evidence map›Paper›PMID 27350129›Full record

ArticleBMC cell biology2016

Specific localization of nesprin-1-α2, the short isoform of nesprin-1 with a KASH domain, in developing, fetal and regenerating muscle, using a new monoclonal antibody.

Ian Holt, Nguyen Thuy Duong, Qiuping Zhang, Le Thanh Lam, Caroline A Sewry, Kamel Mamchaoui, Catherine M Shanahan, Glenn E Morris

Open access · goldAbstract read
In one paragraph

Article in BMC cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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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

8 authors at 4 institutions in 2 countries.

Ian HoltWolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK. ian.holt@rjah.nhs.uk.
Nguyen Thuy DuongWolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
Qiuping ZhangCardiovascular Division, James Black Centre, King's College, London, SE5 9NU, UK.
Le Thanh LamWolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
Caroline A SewryWolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
Kamel MamchaouiSorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, 47 Boulevard de l'hôpital, 75013, Paris, France.
Catherine M ShanahanCardiovascular Division, James Black Centre, King's College, London, SE5 9NU, UK.
Glenn E MorrisWolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK.
Robert Jones and Agnes Hunt Orthopaedic Hospital · GBKing's College London · GBCentre de Recherche en MyologieKeele University · GB

Funding

British Heart Foundation PG/11/58/29004British Heart Foundation PG/11/71/29091British Heart Foundation RG/11/14/29056
6 · The paper itself

Abstract

backgroundNesprin-1-giant (1008kD) is a protein of the outer nuclear membrane that links nuclei to the actin cytoskeleton via amino-terminal calponin homology domains. The short nesprin-1 isoform, nesprin-1-α2, is present only in skeletal and cardiac muscle and several pathogenic mutations occur within it, but the functions of this short isoform without calponin homology domains are unclear. The aim of this study was to determine mRNA levels and protein localization of nesprin-1-α2 at different stages of muscle development in order to shed light on its functions.

resultsmRNA levels of all known nesprin-1 isoforms with a KASH domain were determined by quantitative PCR. The mRNA for the 111 kD muscle-specific short isoform, nesprin-1-α2, was not detected in pre-differentiation human myoblasts but was present at significant levels in multinucleate myotubes. We developed a monoclonal antibody against the unique amino-terminal sequence of nesprin-1-α2, enabling specific immunolocalization for the first time. Nesprin-1-α2 protein was undetectable in pre-differentiation myoblasts but appeared at the nuclear rim in post-mitotic, multinucleate myotubes and reached its highest levels in fetal muscle. In muscle from a Duchenne muscular dystrophy biopsy, nesprin-1-α2 protein was detected mainly in regenerating fibres expressing neonatal myosin. Nesprin-1-giant was present at all developmental stages, but was also highest in fetal and regenerating fibres. In fetal muscle, both isoforms were present in the cytoplasm, as well as at the nuclear rim. A pathogenic early stop codon (E7854X) in nesprin-1 caused reduced mRNA levels and loss of protein levels of both nesprin-1-giant and (unexpectedly) nesprin-1-α2, but did not affect myogenesis in vitro.

conclusionsNesprin-1-α2 mRNA and protein expression is switched on during myogenesis, alongside other known markers of muscle differentiation. The results show that nesprin-1-α2 is dynamically controlled and may be involved in some process occurring during early myofibre formation, such as re-positioning of nuclei.

Indexed as

Muscle DevelopmentRegenerationAdolescentAdultAgedAged, 80 and overAntibodies, MonoclonalCarrier ProteinsCell NucleusCells, CulturedChildChild, PreschoolCytoskeletal ProteinsFemaleFetusHumansAntibodies, MonoclonalCarrier ProteinsCytoskeletal ProteinsMembrane ProteinsNerve Tissue ProteinsPeptidesProtein IsoformsRNA-Binding ProteinsRNA, MessengerSYNE1 protein, humanCardiomyopathyEmery-Dreifuss muscular dystrophyLamin A/CMonoclonal antibodyNuclear membraneSYNE1

Identifiers

PMID27350129
PMCPMC4924313
OpenAlexW2467144999

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.