title: A Rickettsia WASP-like protein activates the Arp2/3 complex and mediates actin-based motility.
abstract: Spotted fever group Rickettsia are obligate intracellular pathogens that exploit the host cell actin cytoskeleton to promote motility and cell-to-cell spread. Although other pathogens such as Listeria monocytogenes use an Arp2/3 complex-dependent nucleation mechanism to generate comet tails consisting of Y-branched filament arrays, Rickettsia polymerize tails consisting of unbranched filaments by a previously unknown mechanism. We identified genes in several Rickettsia species encoding proteins (termed RickA) with similarity to the WASP family of Arp2/3-complex activators. Rickettsia rickettsii RickA activated both the nucleation and Y-branching activities of the Arp2/3 complex like other WASP-family proteins, and was sufficient to direct the motility of microscopic beads in cell extracts. Actin tails generated by RickA-coated beads consisted of Y-branched filament networks. These data suggest that Rickettsia use an Arp2/3 complex-dependent actin-nucleation mechanism similar to that of other pathogens. We propose that additional Rickettsia or host factors reorganize the Y-branched networks into parallel arrays in a manner similar to a recently proposed model of filopodia formation.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jeng
authors.forename: Erin D
authors.initials: ED
authors.lastname: Goley
authors.forename: Joseph A
authors.initials: JA
authors.lastname: D'Alessio
authors.forename: Oleg Y
authors.initials: OY
authors.lastname: Chaga
authors.forename: Tatyana M
authors.initials: TM
authors.lastname: Svitkina
authors.forename: Gary G
authors.initials: GG
authors.lastname: Borisy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Heinzen
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Welch
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D012284:Rickettsia rickettsii / Q000378:metabolism* / Q000472:pathogenicity; D016415:Sequence Alignment; D051300:Wiskott-Aldrich Syndrome Protein Family
chemical_list: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; C491314:RickA protein, Rickettsia; D051300:Wiskott-Aldrich Syndrome Protein Family