Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly

Nat Commun. 2017 Sep 26;8(1):703. doi: 10.1038/s41467-017-00445-3.


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.The fission yeast cytokinetic ring assembles by Search-Capture-Pull-Release from precursor nodes that include formin Cdc12 and myosin Myo2. The authors reconstitute Search-Capture-Pull in vitro and find that Myo2 pulling on Cdc12-associated actin filaments mechano-inhibits Cdc12-mediated assembly, which enables proper ring assembly in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton
  • Actomyosin / genetics
  • Actomyosin / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Fetal Proteins / genetics
  • Fetal Proteins / metabolism
  • Formins
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microscopy, Fluorescence / methods
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Myosin Type II / genetics
  • Myosin Type II / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*


  • Cdc12 protein, S pombe
  • Cytoskeletal Proteins
  • Fetal Proteins
  • Formins
  • MYO2 protein, S pombe
  • Microfilament Proteins
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins
  • Actomyosin
  • Myosin Type II
  • Myosin Heavy Chains