Regulatory mimicry in Listeria monocytogenes actin-based motility.
The actin-based motility of the intracellular pathogen Listeria monocytogenes relies on ActA, a bacterial factor with a structural domain allowing it to mimic the actin nucleation-promoting activity of host cell proteins of the WASP/WAVE family. Here, we used an RNAi-based genetic approach in combination with computer-assisted image analysis to investigate the role of host factors in L. monocytogenes cell-to-cell spread. We showed that the host cell serine/threonine kinase CK2 is required for efficient actin tail formation by L. monocytogenes. Furthermore, CK2-mediated phosphorylation of ActA regulated its affinity for the actin-nucleating ARP2/3 complex, as is the case for CK2-mediated phosphorylation of WASP and WAVE. Thus, ActA not only displays structural mimicry of WASP/WAVE family members, but also regulatory mimicry, having precisely co-opted the host machinery regulating these proteins. Comparisons based on ActA amino acid sequence suggest that unrelated pathogens that display actin-based motility may have evolved a similar strategy of regulatory mimicry.
Chong
Ryan
R
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT, USA.
Swiss
Rachel
R
Briones
Gabriel
G
Stone
Kathryn L
KL
Gulcicek
Erol E
EE
Agaisse
Hervé
H
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008089:Listeria monocytogenes / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008088:Listeriosis / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment
D051376:Actin-Related Protein 2-3 Complex; D001426:Bacterial Proteins; D008565:Membrane Proteins; C072980:actA protein, Listeria monocytogenes; D047390:Casein Kinase II