Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly

• DOI: 10.1038/s41467-017-00445-3
• Publication Date: 2017-09-20T14:30:26Z
• Authors: Dennis Zimmermann; Kaitlin E. Homa; Glen M. Hocky; Luther W. Pollard; Enrique M. De La ...; Gregory A. Voth; Kathleen M. Trybus; David R. Kovar
• Keywords: Fetal Proteins; Myosin Type II; 0303 health sciences; Myosin Heavy Chains; Science; Q; Microfilament Proteins; Formins; Nuclear Proteins; Actomyosin; Article; Actin Cytoskeleton; Cytoskeletal Proteins; 03 medical and health sciences; Microscopy, Fluorescence; Schizosaccharomyces; Schizosaccharomyces pombe Proteins

AbstractCytokinesis 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.