title: An attenuating role of a WASP-related protein, WASP-B, in the regulation of F-actin polymerization and pseudopod formation via the regulation of RacC during Dictyostelium chemotaxis.
abstract: The WASP family of proteins has emerged as important regulators that connect multiple signaling pathways to regulate the actin cytoskeleton. Dictyostelium cells express WASP, as well as a WASP related protein, WASP-B, endoded by wasB gene. WASP-B contains many of the domains present in WASP. Analysis of wild type, wasB null cells revealed that WASP-B is required for proper control of F-actin polymerization in response to a cAMP gradient. Due to the lack of tight control on actin polymerization, wasB null cells exhibited higher level of F-actin polymerization. wasB(-) cells extend more de novo pseudopods laterally and their average life span is longer than those of wild type cells, causing more turns and inefficient chemotaxis. YFP-WASP-B appears to be uniformly distributed in the cytosol and shows no translocation to cortical membrane upon cAMP stimulation. Active RacC pull-down assay reveals that the level of active RacC in wasB(-) cells is significantly higher than wild type cells. Moreover, the distribution of active RacC is not localized in wasB(-) cells. We conclude that chemotaxis defects of wasB(-) cells are likely to result from the aberrant regulation of RacC activation and localization.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA. chang.chung@vanderbilt.edu
authors.forename: Chang Y
authors.initials: CY
authors.lastname: Chung
authors.forename: Alexander
authors.initials: A
authors.lastname: Feoktistov
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hollingsworth
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivero
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Mandel
mesh_terms: D000199:Actins / Q000378:metabolism*; D001704:Biopolymers / Q000378:metabolism*; D002633:Chemotaxis; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*; D011554:Pseudopodia; D013347:Subcellular Fractions / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000502:physiology*
chemical_list: D000199:Actins; D001704:Biopolymers; D015800:Protozoan Proteins; D051316:Wiskott-Aldrich Syndrome Protein; D000242:Cyclic AMP
keywords: Chemotaxis; Dictyostelium; F-actin; WASP