title: Homeostatic actin cytoskeleton networks are regulated by assembly factor competition for monomers.
abstract: Controlling the quantity and size of organelles through competition for a limited supply of components is quickly emerging as an important cellular regulatory mechanism. Cells assemble diverse actin filament (F-actin) networks for fundamental processes including division, motility, and polarization. F-actin polymerization is tightly regulated by activation of assembly factors such as the Arp2/3 complex and formins at specific times and places. We directly tested an additional hypothesis that diverse F-actin networks are in homeostasis, whereby competition for actin monomers (G-actin) is critical for regulating F-actin network size. Here we show that inhibition of Arp2/3 complex in the fission yeast Schizosaccharomyces pombe not only depletes Arp2/3-complex-mediated endocytic actin patches, but also induces a dramatic excess of formin-assembled F-actin. Conversely, disruption of formin increases the density of Arp2/3-complex-mediated patches. Furthermore, modification of actin levels significantly perturbs the fission yeast actin cytoskeleton. Increasing actin favors Arp2/3-complex-mediated actin assembly, whereas decreasing actin favors formin-mediated contractile rings. Therefore, the specific actin concentration in a cell is critical, and competition for G-actin helps regulate the proper amount of F-actin assembly for diverse processes.
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, 920 East 58(th) Street, Chicago, IL 60637, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Burke
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, 920 East 58(th) Street, Chicago, IL 60637, USA.
authors.forename: Jenna R
authors.initials: JR
authors.lastname: Christensen
authors.affiliation: Department of Cell and Developmental Biology, State University of New York (SUNY) Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Barone
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, 920 East 58(th) Street, Chicago, IL 60637, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Suarez
authors.affiliation: Department of Cell and Developmental Biology, State University of New York (SUNY) Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. Electronic address: sirotkiv@upstate.edu.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sirotkin
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, 920 East 58(th) Street, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, 920 East 58(th) Street, Chicago, IL 60637, USA. Electronic address: drkovar@uchicago.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D000080865:Formins; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C531994:Cdc12 protein, S pombe; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C444419:FOR3 protein, S pombe; D000080865:Formins; D008840:Microfilament Proteins; D029702:Schizosaccharomyces pombe Proteins