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Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly

Author

Listed:
  • Dennis Zimmermann

    (The University of Chicago)

  • Kaitlin E. Homa

    (The University of Chicago)

  • Glen M. Hocky

    (The University of Chicago)

  • Luther W. Pollard

    (University of Vermont)

  • Enrique M. De La Cruz

    (Yale University)

  • Gregory A. Voth

    (The University of Chicago)

  • Kathleen M. Trybus

    (University of Vermont)

  • David R. Kovar

    (The University of Chicago
    The University of Chicago)

Abstract

Cytokinesis physically separates dividing cells by forming a contractile actomyosin ring. The fission yeast contractile ring has been proposed to assemble by Search-Capture-Pull-Release from cytokinesis precursor nodes that include the molecular motor type-II myosin Myo2 and the actin assembly factor formin Cdc12. By successfully reconstituting Search-Capture-Pull in vitro, we discovered that formin Cdc12 is a mechanosensor, whereby myosin pulling on formin-bound actin filaments inhibits Cdc12-mediated actin assembly. We mapped Cdc12 mechanoregulation to its formin homology 1 domain, which facilitates delivery of new actin subunits to the elongating actin filament. Quantitative modeling suggests that the pulling force of the myosin propagates through the actin filament, which behaves as an entropic spring, and thereby may stretch the disordered formin homology 1 domain and impede formin-mediated actin filament elongation. Finally, live cell imaging of mechano-insensitive formin mutant cells established that mechanoregulation of formin Cdc12 is required for efficient contractile ring assembly in vivo.

Suggested Citation

  • Dennis Zimmermann & Kaitlin E. Homa & Glen M. Hocky & Luther W. Pollard & Enrique M. De La Cruz & Gregory A. Voth & Kathleen M. Trybus & David R. Kovar, 2017. "Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00445-3
    DOI: 10.1038/s41467-017-00445-3
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    Cited by:

    1. Sayaka Sekine & Mitsusuke Tarama & Housei Wada & Mustafa M. Sami & Tatsuo Shibata & Shigeo Hayashi, 2024. "Emergence of periodic circumferential actin cables from the anisotropic fusion of actin nanoclusters during tubulogenesis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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