title: ADF/cofilin regulates actomyosin assembly through competitive inhibition of myosin II binding to F-actin.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. owiggan@colostate.edu
authors.forename: O'Neil
authors.initials: O
authors.lastname: Wiggan
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Shaw
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: DeLuca
authors.forename: James R
authors.initials: JR
authors.lastname: Bamburg
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D024462:Myosin Type II / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D000205:Actomyosin; D024462:Myosin Type II