Evidence map›Paper›PMID 22893699›Full record

ArticleThe Journal of biological chemistry2012

The small GTPase RhoA regulates the contraction of smooth muscle tissues by catalyzing the assembly of cytoskeletal signaling complexes at membrane adhesion sites.

Wenwu Zhang, Youliang Huang, Susan J Gunst

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

52 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
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  4. Review
  5. Review
  6. Review
  7. Review
  8. Mechanosensitive stem cell fate choice is instructed by dynamic fluctuations in activation of Rho GTPases.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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  11. Vascular mechanotransduction.Physiological reviews · 2023
    Review
  12. Crosstalk between CD4American journal of respiratory and critical care medicine · 2023
    Article
  13. Article
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  16. Dynamic cytosolic CaAmerican journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  17. Article
  18. Effects of TNFα on Dynamic Cytosolic CaFrontiers in physiology · 2021
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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

3 authors at 1 institution in 1 country.

Wenwu ZhangDepartment of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Youliang Huang
Susan J Gunst
Indiana University School of Medicine

Funding

Smooth Muscle Mechanisms in Dynamic Airways PropertiesR01HL029289 · NHLBI · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI GUNST, SUSAN J. · 1986 to 2020
$7.3M
Regulation of Actin Dynamics in Airway Smooth MuscleR01HL074099 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI GUNST, SUSAN J. · 2003 to 2011
$3.2M
Targeting actin dynamics to inhibit airway hypperresponsiveness and inflammationR01HL109629 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI GUNST, SUSAN J., TEPPER, ROBERT S. · 2013 to 2016
$2.1M
SMOOTH MUSCLE MECHANISMS IN DYNAMIC AIRWAY PROPERTIESR23HL029289 · NHLBI · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI GUNST, SUSAN J. · 1985 to 1985
–
NHLBI NIH HHS HL074099NHLBI NIH HHS HL-29289NHLBI NIH HHS R01 HL029289NHLBI NIH HHS R01 HL074099NHLBI NIH HHS R01 HL109629
6 · The paper itself

Abstract

The activation of the small GTPase RhoA is necessary for ACh-induced actin polymerization and airway smooth muscle (ASM) contraction, but the mechanism by which it regulates these events is unknown. Actin polymerization in ASM is catalyzed by the actin filament nucleation activator, N-WASp and the polymerization catalyst, Arp2/3 complex. Activation of the small GTPase cdc42, a specific N-WASp activator, is also required for actin polymerization and tension generation. We assessed the mechanism by which RhoA regulates actin dynamics and smooth muscle contraction by expressing the dominant negative mutants RhoA T19N and cdc42 T17N, and non-phosphorylatable paxillin Y118/31F and paxillin ΔLD4 deletion mutants in SM tissues. Their effects were evaluated in muscle tissue extracts and freshly dissociated SM cells. Protein interactions and cellular localization were analyzed using proximity ligation assays (PLA), immunofluorescence, and GTPase and kinase assays. RhoA inhibition prevented ACh-induced cdc42 activation, N-WASp activation and the interaction of N-WASp with the Arp2/3 complex at the cell membrane. ACh induced paxillin phosphorylation and its association with the cdc42 GEFS, DOCK180 and α/βPIX. Paxillin tyrosine phosphorylation and its association with βPIX were RhoA-dependent, and were required for cdc42 activation. The ACh-induced recruitment of paxillin and FAK to the cell membrane was dependent on RhoA. We conclude that RhoA regulates the contraction of ASM by catalyzing the assembly and activation of cytoskeletal signaling modules at membrane adhesomes that initiate signaling cascades that regulate actin polymerization and tension development in response to contractile agonist stimulation. Our results suggest that the RhoA-mediated assembly of adhesome complexes is a fundamental step in the signal transduction process in response to agonist -induced smooth muscle contraction.

Indexed as

AcetylcholineActin-Related Protein 2-3 ComplexActinsAmino Acid SubstitutionAnimalscdc42 GTP-Binding ProteinCell MembraneChickensCytoskeletonDogsHumansMuscle ContractionMuscle, SmoothMutation, MissensePaxillinrhoA GTP-Binding ProteinAcetylcholineActin-Related Protein 2-3 ComplexActinscdc42 GTP-Binding ProteinPaxillinPXN protein, humanrhoA GTP-Binding ProteinRHOA protein, humanWASL protein, humanWiskott-Aldrich Syndrome Protein, Neuronal

Identifiers

PMID22893699
PMCPMC3464510
OpenAlexW2049263539

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.