ADF/cofilin Regulates Actomyosin Assembly Through Competitive Inhibition of Myosin II Binding to F-actin

Dev Cell. 2012 Mar 13;22(3):530-43. doi: 10.1016/j.devcel.2011.12.026.

Abstract

The contractile actin cortex is important for diverse fundamental cell processes, but little is known about how the assembly of F-actin and myosin II motors is regulated. We report that depletion of actin depolymerizing factor (ADF)/cofilin proteins in human cells causes increased contractile cortical actomyosin assembly. Remarkably, our data reveal that the major cellular defects resulting from ADF/cofilin depletion, including cortical F-actin accumulation, were largely due to excessive myosin II activity. We identify that ADF/cofilins from unicellular organisms to humans share a conserved activity to inhibit myosin II binding to F-actin, indicating a mechanistic rationale for our cellular results. Our study establishes an essential requirement for ADF/cofilin proteins in the control of normal cortical contractility and in processes such as mitotic karyokinesis. We propose that ADF/cofilin proteins are necessary for controlling actomyosin assembly and intracellular contractile force generation, a function of equal physiological importance to their established roles in mediating F-actin turnover.

Publication types

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

MeSH terms

  • Actin Depolymerizing Factors / metabolism*
  • Actins / metabolism*
  • Actomyosin / metabolism*
  • HeLa Cells
  • Humans
  • Myosin Type II / metabolism*
  • Protein Binding

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Actomyosin
  • Myosin Type II