title: A molecular pathway for myosin II recruitment to stress fibers.
abstract: BACKGROUND
  Cell migration and morphogenesis are driven by both protrusive and contractile actin filament structures. The assembly mechanisms of lamellipodial and filopodial actin filament arrays, which provide the force for plasma membrane protrusions through actin filament treadmilling, are relatively well understood. In contrast, the mechanisms by which contractile actomyosin arrays such as stress fibers are generated in cells, and how myosin II is specifically recruited to these structures, are not known.
  
  
  RESULTS
  We demonstrate that four functionally distinct tropomyosins are required for assembly of stress fibers in cultured osteosarcoma cells. Tm1, Tm2/3, and Tm5NM1/2 stabilize actin filaments at distinct stress fiber regions. In contrast, Tm4 promotes stress fiber assembly by recruiting myosin II to stress fiber precursors. Elimination of any one of the tropomyosins fatally compromises stress fiber formation. Importantly, Dia2 formin is critical to stress fiber assembly by nucleating Tm4-decorated actin filaments at the cell cortex. Myosin II is specifically recruited through a Tm4-dependent mechanism to the Dia2-nucleated filaments, which subsequently assemble endwise with Arp2/3-nucleated actin filament structures to yield contractile stress fibers.
  
  
  CONCLUSIONS
  These experiments identified a pathway, involving Dia2- and Arp2/3-promoted actin filament nucleation and several functionally distinct tropomyosins, that is required for generation of contractile actomyosin arrays in cells.
authors: Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
authors: Sari
authors: S
authors: Tojkander
authors: Gergana
authors: G
authors: Gateva
authors: Galina
authors: G
authors: Schevzov
authors: Pirta
authors: P
authors: Hotulainen
authors: Perttu
authors: P
authors: Naumanen
authors: Claire
authors: C
authors: Martin
authors: Peter W
authors: PW
authors: Gunning
authors: Pekka
authors: P
authors: Lappalainen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D003285:Contractile Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009024:Morphogenesis; D024462:Myosin Type II / Q000378:metabolism*; D012516:Osteosarcoma; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D022502:Stress Fibers / Q000378:metabolism*; D014335:Tropomyosin / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003285:Contractile Proteins; C108962:DIAPH1 protein, human; C491462:DIAPH2 protein, human; D000080865:Formins; D008565:Membrane Proteins; D020033:Protein Isoforms; D014335:Tropomyosin; D000205:Actomyosin; D024462:Myosin Type II