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.

Details

Title
Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly
Author
Zimmermann, Dennis 1 ; Homa, Kaitlin E 1 ; Hocky, Glen M 2 ; Pollard, Luther W 3 ; Enrique M De La Cruz 4 ; Voth, Gregory A 2 ; Trybus, Kathleen M 3 ; Kovar, David R 5 

 Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA 
 Department of Chemistry, The James Franck Institute and Institute for Biophysical Dynamics and Computation Institute, The University of Chicago, Chicago, IL, USA 
 Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT, USA 
 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA 
 Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA 
Pages
1-13
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1943086842
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.