title: Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation.
abstract: Cell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In two-dimensional migration, protrusion of these thin sheets of cytoplasm is considered relevant to both exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodium formation can be potently stimulated by Rho GTPases of the Rac subfamily, but also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac-deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac - although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signaling is essential for lamellipodium protrusion and for efficient cell migration, but not for spreading or filopodium formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.
authors.affiliation: Institute of Genetics, University of Bonn, Karlrobert-Kreiten Strasse 13, D-53115 Bonn, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Steffen
authors.forename: Markus
authors.initials: M
authors.lastname: Ladwein
authors.forename: Georgi A
authors.initials: GA
authors.lastname: Dimchev
authors.forename: Anke
authors.initials: A
authors.lastname: Hein
authors.forename: Lisa
authors.initials: L
authors.lastname: Schwenkmezger
authors.forename: Stefan
authors.initials: S
authors.lastname: Arens
authors.forename: Kathrin I
authors.initials: KI
authors.lastname: Ladwein
authors.forename: J
authors.initials: J
authors.lastname: Margit Holleboom
authors.forename: Florian
authors.initials: F
authors.lastname: Schur
authors.forename: J
authors.initials: J
authors.lastname: Victor Small
authors.forename: Janett
authors.initials: J
authors.lastname: Schwarz
authors.forename: Ralf
authors.initials: R
authors.lastname: Gerhard
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
authors.forename: Theresia E B
authors.initials: TE
authors.lastname: Stradal
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Klemens
authors.initials: K
authors.lastname: Rottner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology*; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein
keywords: Actin; Adhesion; CAAX; Chemotaxis; Filopodia; Lamellipodia; Migration; Rac1
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