title: Vav1 and Vav2 play different roles in macrophage migration and cytoskeletal organization.
abstract: Vav family proteins act as guanine nucleotide exchange factors for Rho family proteins, which are known to orchestrate cytoskeletal changes and cell migration in response to extracellular stimuli. Using mice deficient for Vav1, Vav2 and/or Vav3, overlapping and isoform-specific functions of the three Vav proteins have been described in various hematopoietic cell types, but their roles in regulating cell morphology and migration have not been studied in detail. To investigate whether Vav isoforms have redundant or unique functions in regulating adhesion and migration, we investigated the properties of Vav1-deficient and Vav2-deficient macrophages. Both Vav1-deficient and Vav2-deficient cells have a smaller adhesive area; yet, only Vav1-deficient cells have a reduced migration speed, which coincides with a lower level of microtubules. Vav2-deficient macrophages display a high level of constitutive membrane ruffling, but neither Vav1 nor Vav2 is required for colony stimulating factor-1-induced membrane ruffling and cell spreading. Our results suggest that the migration speed of macrophages is regulated independently of spread area or membrane ruffling and that Vav1 is selectively required to maintain a normal migration speed.
authors.affiliation: Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, 91 Riding House Street, London W1W 7BS, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Wells
authors.forename: Parag J
authors.initials: PJ
authors.lastname: Bhavsar
authors.forename: Iwan R
authors.initials: IR
authors.lastname: Evans
authors.forename: Elena
authors.initials: E
authors.lastname: Vigorito
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.forename: Victor
authors.initials: V
authors.lastname: Tybulewicz
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000648:ultrastructure*; D008264:Macrophages / Q000276:immunology* / Q000648:ultrastructure*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D003598:Cytoskeletal Proteins; D051567:Proto-Oncogene Proteins c-vav; D014404:Tubulin; C496619:Vav1 protein, mouse; C490565:Vav2 protein, mouse