Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly

Dennis Zimmermann, Kaitlin E. Homa, Glen Hocky, Luther W. Pollard, Enrique M. De La Cruz, Gregory A. Voth, Kathleen M. Trybus, David R. Kovar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number703
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Actomyosin
Actin Cytoskeleton
myosins
Actins
filaments
assembly
Cytokinesis
rings
pulling
homology
Myosins
cells
Myosin Type II
Schizosaccharomyces
yeast
elongation
fission
delivery
Yeast
Elongation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zimmermann, D., Homa, K. E., Hocky, G., Pollard, L. W., De La Cruz, E. M., Voth, G. A., ... Kovar, D. R. (2017). Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly. Nature Communications, 8(1), [703]. https://doi.org/10.1038/s41467-017-00445-3

Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly. / Zimmermann, Dennis; Homa, Kaitlin E.; Hocky, Glen; Pollard, Luther W.; De La Cruz, Enrique M.; Voth, Gregory A.; Trybus, Kathleen M.; Kovar, David R.

In: Nature Communications, Vol. 8, No. 1, 703, 01.12.2017.

Research output: Contribution to journalArticle

Zimmermann, D, Homa, KE, Hocky, G, Pollard, LW, De La Cruz, EM, Voth, GA, Trybus, KM & Kovar, DR 2017, 'Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly', Nature Communications, vol. 8, no. 1, 703. https://doi.org/10.1038/s41467-017-00445-3
Zimmermann, Dennis ; Homa, Kaitlin E. ; Hocky, Glen ; Pollard, Luther W. ; De La Cruz, Enrique M. ; Voth, Gregory A. ; Trybus, Kathleen M. ; Kovar, David R. / Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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