Rickettsia Sca4 Reduces Vinculin-Mediated Intercellular Tension to Promote Spread.
Cell
; 167(3): 670-683.e10, 2016 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-27768890
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Rickettsia
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Infecciones por Rickettsia
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Proteínas Bacterianas
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Vinculina
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Mecanotransducción Celular
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Interacciones Huésped-Patógeno
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Antígenos Bacterianos
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2016
Tipo del documento:
Article