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Publication

Rickettsia Sca4 Reduces Vinculin-Mediated Intercellular Tension to Promote Spread.

Cell | 2016

Spotted fever group (SFG) rickettsiae are human pathogens that infect cells in the vasculature. They disseminate through host tissues by a process of cell-to-cell spread that involves protrusion formation, engulfment, and vacuolar escape. Other bacterial pathogens rely on actin-based motility to provide a physical force for spread. Here, we show that SFG species Rickettsia parkeri typically lack actin tails during spread and instead manipulate host intercellular tension and mechanotransduction to promote spread. Using transposon mutagenesis, we identified surface cell antigen 4 (Sca4) as a secreted effector of spread that specifically promotes protrusion engulfment. Sca4 interacts with the cell-adhesion protein vinculin and blocks association with vinculin's binding partner, α-catenin. Using traction and monolayer stress microscopy, we show that Sca4 reduces vinculin-dependent mechanotransduction at cell-cell junctions. Our results suggest that Sca4 relieves intercellular tension to promote protrusion engulfment, which represents a distinctive strategy for manipulating cytoskeletal force generation to enable spread.

Pubmed ID: 27768890 RIS Download

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uManager (RRID:SCR_000415)

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Associated grants

Agency: NIGMS NIH HHS, United States
Id: R00 GM115765
Agency: NIGMS NIH HHS, United States
Id: P50 GM107615
Agency: NIAID NIH HHS, United States
Id: R21 AI109270
Agency: NCRR NIH HHS, United States
Id: S10 RR027696
Agency: NIAID NIH HHS, United States
Id: R37 AI036929
Agency: Howard Hughes Medical Institute, United States
Agency: NIAID NIH HHS, United States
Id: R01 AI109044
Agency: NIGMS NIH HHS, United States
Id: K99 GM115765
Agency: NIGMS NIH HHS, United States
Id: R01 GM084227
Agency: NHLBI NIH HHS, United States
Id: R01 HL128630

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uManager (tool)

RRID:SCR_000415

Software package for control of automated microscopes. Cross-platform desktop application, to control motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories.

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