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Cited by 958Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingGenomics and Chromatin Dynamics

Linking actin dynamics and gene transcription to drive cellular motile functions

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Olson, Eric N., Nordheim, Alfred·2010·Nature Reviews Molecular Cell Biology
DOI 10.1038/nrm2890PMC PMC3073350
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Abstract

Numerous physiological and pathological stimuli promote the rearrangement of the actin cytoskeleton, thereby modulating cellular motile functions. Although it seems intuitively obvious that cell motility requires coordinated protein biosynthesis, until recently the linkage between cytoskeletal actin dynamics and correlated gene activities remained unknown. This knowledge gap was filled in part by the discovery that globular actin polymerization liberates myocardin-related transcription factor (MRTF) cofactors, thereby inducing the nuclear transcription factor serum response factor (SRF) to modulate the expression of genes encoding structural and regulatory effectors of actin dynamics. This insight stimulated research to better understand the actin-MRTF-SRF circuit and to identify alternative mechanisms that link cytoskeletal dynamics and genome activity.

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  • MRTFA and MRTFB are transcriptional cofactors that respond to actin polymerisation and regulate contractility, fibrogenesis and epithelial-mesenchymal transition.

    “Proteins known as myocardin‐related transcription factor A and B (MRTFA and MRTFB) are transcriptional cofactors that respond to actin polymerisation, and regulate contractility, fibrogenesis and epithelial‐mesenchymal transition (EMT) [8];”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [8]

    The MRTF–SRF circuit sections identify MRTF-A and MRTF-B as transcriptional co-activators responsive to actin polymerisation, and the contractile-genes section links MRTF-regulated genes to muscle contractile functions. The Conclusions and future directions section says the circuit is expected to contribute to EMT, which is more tentative than the claim that it regulates EMT. No passage found supports the fibrogenesis part of the claim (searched: fibrogenesis, fibrosis, fibrotic and myofibroblast). (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ACTB gene is transcriptionally regulated by MRTFs.

    “ACTB protein was upregulated, and this correlated with the presence of stress fibres after 72 h of culture (Fig. 4B); ACTB gene is transcriptionally regulated by MRTFs [8].”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [8]

    The MRTF–SRF circuit section (page not available in our copy) says that actin genes are under MRTF–SRF control, supporting the general transcriptional-regulation claim. The passages do not identify ACTB specifically, so they do not establish that this particular actin gene is regulated by MRTFs. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The increase in traction forces may be explained by the increase of actin cytoskeleton-related proteins, such as ACTB and ITGB1, in PH cultured at stiff HGs (10 kPa), where MRTFA, YAP and TAZ proteins are translocated in the nucleus.

    “This may be explained by the increase of actin cytoskeleton‐related proteins, such as ACTB and ITGB1, in PH cultured at stiff HGs (10 kPa), where MRTFA, YAP and TAZ proteins are translocated in the nucleus [8, 9].”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [8]

    The section ‘Actin-mediated regulation of MRTF nuclear shuttling’ says actin polymerization permits MRTF nuclear import. ‘Genes affecting actin dynamics and cell motility’ links MRTF–SRF regulation to actin and integrin-related genes. The review does not establish YAP or TAZ nuclear translocation, or the proposed explanation for increased traction forces in PH cultured on 10 kPa hydrogels. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • SRF, ACTB, CAV1, ITGB1, FHL2 and LMNA/C proteins depend on MRTcoF transcriptionally.

    “all these proteins depend on MRTcoF transcriptionally [8].”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [8]

    In “MRTF–SRF target gene functions > Genes affecting actin dynamics and cell motility” (page unavailable), the review identifies β1 integrin (ITGB1) as encoded by an SRF–MRTF-regulated gene and describes actin as an SRF-regulated gene product. It also calls FHL2 an SRF-regulated gene in “Microfilament-to-genome relay systems > LIM domain-containing proteins” (page unavailable), but does not establish MRTF dependence for FHL2 or specifically identify ACTB. The passages do not establish that SRF, CAV1, or LMNA/C depend transcriptionally on MRTF cofactors. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Olson, E. N., & Nordheim, A.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • University of Tübingen (DE)
Corresponding author
Nordheim, Alfred
ORCID
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2010-05
Volume
11
Issue
5
Pages
353-365
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/nrm2890
PMC
PMC3073350
OpenAlex
W2090392605
Cited by
958
References
7
Citations by year
2026: 33 · 2025: 38 · 2024: 44 · 2023: 51 · 2022: 74 · 2021: 80 · 2020: 84 · 2019: 59 · 2018: 64 · 2017: 80 · 2016: 68 · 2015: 62 · 2014: 61 · 2013: 59 · 2012: 47
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • National Heart, Lung, and Blood Institute (R01HL093039)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
actin dynamics, gene transcription, cell motility, MRTF, serum response factor, actin polymerization, actin cytoskeleton, transcriptional regulation
MeSH terms
Actins, Animals, Cell Movement, Humans, Transcription, Genetic, Signal Transduction, Trans-Activators, Serum Response Factor

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