Rickettsia Sca4 Reduces Vinculin-Mediated Intercellular Tension to Promote Spread
| Autor: | Juan C. del Álamo, Effie Bastounis, Natasha M. Kafai, Matthew D. Welch, Julie A. Theriot, Rebecca L. Lamason, Ricardo Serrano |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mechanotransduction listeria monocytogenes sca4 cell-to-cell spread Medical and Health Sciences Mechanotransduction Cellular host-pathogen interactions Rickettsia Cytoskeleton Tumor biology Effector Bacterial cytoskeleton Biological Sciences Vinculin Cadherins 3. Good health Cell biology Host-Pathogen Interactions intercellular tension Infection rickettsia parkeri Fever Alpha catenin Motility General Biochemistry Genetics and Molecular Biology Cell Line actin-based motility Vaccine Related 03 medical and health sciences Bacterial Proteins Insertional Cell Line Tumor Cell Adhesion Humans Amino Acid Sequence Antigens Cell adhesion Actin Antigens Bacterial vinculin Prevention Rickettsia Infections Actins Vector-Borne Diseases Mutagenesis Insertional Emerging Infectious Diseases 030104 developmental biology Mutagenesis Mutation biology.protein DNA Transposable Elements Cellular alpha Catenin Developmental Biology |
| Zdroj: | Cell, vol 167, iss 3 |
| ISSN: | 1097-4172 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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