Control of actin turnover by a salmonella invasion protein.
Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein that enhances uptake efficiency by promoting actin polymerization. SipA-bound actin filaments (F-actin) are also resistant to artificial disassembly in vitro. Using biochemical assays of actin dynamics and actin-based motility models, we demonstrate that SipA directly arrests cellular mechanisms of actin turnover. SipA inhibits ADF/cofilin-directed depolymerization both by preventing binding of ADF and cofilin and by displacing them from F-actin. SipA also protects F-actin from gelsolin-directed severing and reanneals gelsolin-severed F-actin fragments. These data suggest that SipA focuses host cytoskeletal reorganization by locally inhibiting both ADF/cofilin- and gelsolin-directed actin disassembly, while simultaneously stimulating pathogen-induced actin polymerization.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Emma J
EJ
McGhie
Richard D
RD
Hayward
Vassilis
V
Koronakis
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002457:Cell Extracts; D003599:Cytoskeleton / Q000378:metabolism; D051345:Destrin; D018260:Gelsolin / Q000378:metabolism; D006790:Host-Parasite Interactions; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012475:Salmonella / Q000472:pathogenicity*; D014981:Xenopus
D051339:Actin Depolymerizing Factors; D000199:Actins; D001426:Bacterial Proteins; D002457:Cell Extracts; D051345:Destrin; D018260:Gelsolin; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C118287:SipA protein, Salmonella