Evidence map›Paper›PMID 21622574›Full record

ArticleThe Journal of biological chemistry2011

Skeletal muscle differentiation and fusion are regulated by the BAR-containing Rho-GTPase-activating protein (Rho-GAP), GRAF1.

Jason T Doherty, Kaitlin C Lenhart, Morgan V Cameron, Christopher P Mack, Frank L Conlon, Joan M Taylor

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
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  20. RNAi Screen inG3 (Bethesda, Md.) · 2019
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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

6 authors at 1 institution in 1 country.

Jason T DohertyFrom the Departments of Pathology and Laboratory Medicine.
Kaitlin C Lenhart
Morgan V Cameron
Christopher P Mack
Frank L Conlon
Joan M Taylor
University of North Carolina at Chapel Hill · US

Funding

Pre-doctoral Training Program in Integrative Vascular BiologyT32HL069768 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher P. Mack · 2002 to 2026
$9.7M
Regulation of Smooth Muscle Differentiation by RhoAR01HL070953 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MACK, CHRISTOPHER P. · 2002 to 2012
$2.8M
FAK Signaling in cardiac growth and hypertrophyR01HL081844 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TAYLOR, JOAN M · 2005 to 2013
$2.6M
Craniofacial and cardiac development in Xenopus: A genetic approachR01DE018825 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CONLON, FRANK LEO, KHOKHA, MUSTAFA K · 2009 to 2013
$2.3M
TBX5 and cardiac proliferationR01HL089641 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CONLON, FRANK LEO · 2008 to 2011
$1.5M
UNC Developmental Biology Training ProgramT32HD046369 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MAGNUSON, TERRY R · 2005 to 2009
$1.4M
Smooth muscle adhesion and plasticity in coronary and outflow tract developmentR01HL102446 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TAYLOR, JOAN M · 2010 to 2013
$1.3M
Adhesion Signaling in Vascular Growth and DevelopmentR01HL071054 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TAYLOR, JOAN M. · 2003 to 2006
$1.2M
NHLBI NIH HHS HL-070953NHLBI NIH HHS HL-071054NHLBI NIH HHS HL-081844NHLBI NIH HHS HL-089641NHLBI NIH HHS R01 HL070953NHLBI NIH HHS R01 HL071054NHLBI NIH HHS R01 HL081844NHLBI NIH HHS R01 HL089641NHLBI NIH HHS R01 HL102446NHLBI NIH HHS T32 HL069768NHLBI NIH HHS T32HL69768NICHD NIH HHS T32 HD046369NICHD NIH HHS T32 HD046369-05NIDCR NIH HHS DE-018825NIDCR NIH HHS R01 DE018825
6 · The paper itself

Abstract

Although RhoA activity is necessary for promoting myogenic mesenchymal stem cell fates, recent studies in cultured cells suggest that down-regulation of RhoA activity in specified myoblasts is required for subsequent differentiation and myotube formation. However, whether this phenomenon occurs in vivo and which Rho modifiers control these later events remain unclear. We found that expression of the Rho-GTPase-activating protein, GRAF1, was transiently up-regulated during myogenesis, and studies in C2C12 cells revealed that GRAF1 is necessary and sufficient for mediating RhoA down-regulation and inducing muscle differentiation. Moreover, forced expression of GRAF1 in pre-differentiated myoblasts drives robust muscle fusion by a process that requires GTPase-activating protein-dependent actin remodeling and BAR-dependent membrane binding or sculpting. Moreover, morpholino-based knockdown studies in Xenopus laevis determined that GRAF1 expression is critical for muscle development. GRAF1-depleted embryos exhibited elevated RhoA activity and defective myofibrillogenesis that resulted in progressive muscle degeneration, defective motility, and embryonic lethality. Our results are the first to identify a GTPase-activating protein that regulates muscle maturation and to highlight the functional importance of BAR domains in myotube formation.

Indexed as

Cell DifferentiationActinsAnimalsBase SequenceCell FusionCell LineCell MembraneEmbryo, NonmammalianGene Expression RegulationGTPase-Activating ProteinsHumansLarvaLipid MetabolismMiceMuscle Fibers, SkeletalMuscle, SkeletalActinsARHGAP26 protein, humanGTPase-Activating Proteinsrho GTP-Binding ProteinsXenopus Proteins

Identifiers

PMID21622574
PMCPMC3138304
OpenAlexW2035597871

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.