Regulation of the formin Bnr1 by septins anda MARK/Par1-family septin-associated kinase.
Formin-family proteins promote the assembly of linear actin filaments and are required to generate cellular actin structures, such as actin stress fibers and the cytokinetic actomyosin contractile ring. Many formin proteins are regulated by an autoinhibition mechanism involving intramolecular binding of a Diaphanous inhibitory domain and a Diaphanous autoregulatory domain. However, the activation mechanism for these Diaphanous-related formins (DRFs) is not completely understood. Although small GTPases play an important role in relieving autoinhibition, other factors likely contribute. Here we describe a requirement for the septin Shs1 and the septin-associated kinase Gin4 for the localization and in vivo activity of the budding yeast DRF Bnr1. In budding yeast strains in which the other formin, Bni1, is conditionally inactivated, the loss of Gin4 or Shs1 results in the loss of actin cables and cell death, similar to the loss of Bnr1. The defects in these strains can be suppressed by constitutive activation of Bnr1. Gin4 is involved in both the localization and activation of Bnr1, whereas the septin Shs1 is required for Bnr1 activation but not its localization. Gin4 promotes the activity of Bnr1 independently of the Gin4 kinase activity, and Gin4 lacking its kinase domain binds to the critical localization region of Bnr1. These data reveal novel regulatory links between the actin and septin cytoskeletons.
Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Shawnna M
SM
Buttery
Keiko
K
Kono
Ema
E
Stokasimov
David
D
Pellman
D000199:Actins / Q000378:metabolism; D016764:Cell Polarity; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D058112:Septins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000199:Actins; C106463:BNR1 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; C107283:GIN4 protein, S cerevisiae; D018844:Cyclin-Dependent Kinases; D058112:Septins