title: Assembly of non-contractile dorsal stress fibers requires α-actinin-1 and Rac1 in migrating and spreading cells.
abstract: Cell migration and spreading is driven by actin polymerization and actin stress fibers. Actin stress fibers are considered to contain α-actinin crosslinkers and nonmuscle myosin II motors. Although several actin stress fiber subtypes have been identified in migrating and spreading cells, the degree of molecular diversity of their composition and the signaling pathways regulating fiber subtypes remain largely uncharacterized. In the present study we identify that dorsal stress fiber assembly requires α-actinin-1. Loss of dorsal stress fibers in α-actinin-1-depleted cells results in defective maturation of leading edge focal adhesions. This is accompanied by a delay in early cell spreading and slower cell migration without noticeable alterations in myosin light chain phosphorylation. In agreement with the unaltered myosin II activity, dorsal stress fiber trunks lack myosin II and are resistant to myosin II ATPase inhibition. Furthermore, the non-contractility of dorsal stress fibers is supported by the finding that Rac1 induces dorsal stress fiber assembly whereas contractile ventral stress fibers are induced by RhoA. Loss of dorsal stress fibers either by depleting α-actinin-1 or Rac1 results in a β-actin accumulation at the leading edge in migrating and spreading cells. These findings molecularly specify dorsal stress fibers from other actin stress fiber subtypes. Furthermore, we propose that non-contractile dorsal stress fibers promote cell migration and early cell spreading through Rac1-induced actin polymerization.
authors.affiliation: Genome-Scale Biology Program, University of Helsinki, P.O. Box 63, Helsinki 00014, Finland.
authors.forename: Bianca
authors.initials: B
authors.lastname: Kovac
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Teo
authors.forename: Tomi P
authors.initials: TP
authors.lastname: Mäkelä
authors.forename: Tea
authors.initials: T
authors.lastname: Vallenius
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D009218:Myosins / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000185:Actinin; D009218:Myosins; D020830:rac1 GTP-Binding Protein