title: Role of Rac in controlling the actin cytoskeleton and chemotaxis in motile cells.
abstract: We have used the chemotactic ability of Dictyostelium cells to examine the roles of Rho family members, known regulators of the assembly of F-actin, in cell movement. Wild-type cells polarize with a leading edge enriched in F-actin toward a chemoattractant. Overexpression of constitutively active Dictyostelium Rac1B(61L) or disruption of DdRacGAP1, which encodes a Dictyostelium Rac1 GAP, induces membrane ruffles enriched with actin filaments around the perimeter of the cell and increased levels of F-actin in resting cells. Whereas wild-type cells move linearly toward the cAMP source, Rac1B(61L) and Ddracgap1 null cells make many wrong turns and chemotaxis is inefficient, which presumably results from the unregulated activation of F-actin assembly and pseudopod extension. Cells expressing dominant-negative DdRac1B(17N) do not have a well-defined F-actin-rich leading edge and do not protrude pseudopodia, resulting in very poor cell motility. From these studies and assays examining chemoattractant-mediated F-actin assembly, we suggest DdRac1 regulates the basal levels of F-actin assembly, its dynamic reorganization in response to chemoattractants, and cellular polarity during chemotaxis.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biology, Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0634, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Chung
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Briscoe
authors.forename: C
authors.initials: C
authors.lastname: Ellsworth
authors.forename: R A
authors.initials: RA
authors.lastname: Firtel
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D002449:Cell Aggregation; D002633:Chemotaxis / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D004023:Dictyostelium / Q000235:genetics / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000242:Cyclic AMP; D020830:rac1 GTP-Binding Protein