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Cited by 34Circadian rhythm and melatoninCellular Mechanics and InteractionsLight effects on plants

The actin cytoskeleton-MRTF/SRF cascade transduces cellular physical niche cues to entrain the circadian clock

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Xiong, Xuekai, Li, Weini, Nam, Jin, Qu, Meng, Kay, Steve A., Ma, Ke·2022·Journal of Cell Science
DOI 10.1242/jcs.260094PMC PMC10658898
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Abstract

The circadian clock is entrained to daily environmental cues. Integrin-linked signaling via actin cytoskeleton dynamics transduces physical niche cues from the extracellular matrix to myocardin-related transcription factor (MRTF)/serum response factor (SRF)-mediated transcription. The actin cytoskeleton organization and SRF-MRTF activity display diurnal oscillations. By interrogating disparate upstream events in the actin cytoskeleton-MRTF-A/SRF signaling cascade, we show that this pathway transduces extracellular niche cues to modulate circadian clock function. Pharmacological inhibition of MRTF-A/SRF by disrupting actin polymerization or blocking the ROCK kinase induced period lengthening with augmented clock amplitude, and genetic loss of function of Srf or Mrtfa mimicked the effects of treatment with actin-depolymerizing agents. In contrast, actin polymerization shortened circadian clock period and attenuated clock amplitude. Moreover, interfering with the cell–matrix interaction through blockade of integrin, inhibition of focal adhesion kinase (FAK, encoded by Ptk2) or attenuating matrix rigidity reduced the period length while enhancing amplitude. Mechanistically, we identified that the core clock repressors Per2, Nr1d1 and Nfil3 are direct transcriptional targets of MRTF-A/SRF in mediating actin dynamics-induced clock response. Collectively, our findings defined an integrin-actin cytoskeleton-MRTF/SRF pathway in linking clock entrainment with extracellular cues that might facilitate cellular adaptation to the physical niche environment.

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  • Regulators of the circadian clock are highly associated with liver metabolism and are known to be regulated by MRTFs.

    “Regulators of the circadian clock are highly associated with liver metabolism and are known to be regulated by MRTFs [56, 57, 58].”

    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 [57]

    The section “MRTF and SRF exert direct transcriptional control of core clock regulators” reports MRTF/SRF regulation of clock genes, including Nr1d1 and Per2. The Introduction and Discussion connect circadian clocks with metabolic disorders and potential metabolic regulation, but do not establish that these regulators are highly associated specifically with liver metabolism. No page numbers are available in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Xiong, X., Li, W., Nam, J., Qu, M., Kay, S. A., & Ma, K.
Affiliations
  • City Of Hope National Medical Center (US)
  • University of California, Riverside (US)
  • University of Southern California (US)
Corresponding author
Ma, Ke
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2022-10-01
Volume
135
Issue
19
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.260094
PMC
PMC10658898
OpenAlex
W4295259889
Cited by
34
References
4
Citations by year
2026: 13 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 1
FWCI
2.77
Type
journal article
Language
en
Open access
Licence
www.biologists.com/user-licence-1-1/ (vor)
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute
  • Comprehensive Cancer Center, City of Hope
  • National Cancer Center
  • National Institutes of Health (1R01DK112794)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
Keywords
circadian clock, clock entrainment, actin cytoskeleton, integrin signaling, extracellular matrix, cell-matrix interactions, focal adhesion kinase, matrix rigidity, actin polymerization, ROCK kinase, Per2, NR1D1, NFIL3, transcriptional regulation
MeSH terms
Myocardin, Actins, Cues, Actin Cytoskeleton, Nuclear Proteins, Transcription Factors, Trans-Activators, Integrins, Serum Response Factor, Circadian Clocks

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