A Rickettsia WASP-like protein activates the Arp2/3 complex and mediates actin-based motility.
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.
Jeng
Robert L
RL
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Goley
Erin D
ED
D'Alessio
Joseph A
JA
Chaga
Oleg Y
OY
Svitkina
Tatyana M
TM
Borisy
Gary G
GG
Heinzen
Robert A
RA
Welch
Matthew D
MD
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
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