Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens.
dc.contributor.author | Hoffmann, Christine | |
dc.contributor.author | Berking, Anne | |
dc.contributor.author | Agerer, Franziska | |
dc.contributor.author | Buntru, Alexander | |
dc.contributor.author | Neske, Florian | |
dc.contributor.author | Chhatwal, G Singh | |
dc.contributor.author | Ohlsen, Knut | |
dc.contributor.author | Hauck, Christof R | |
dc.date.accessioned | 2011-01-04T15:30:24Z | |
dc.date.available | 2011-01-04T15:30:24Z | |
dc.date.issued | 2010-12-15 | |
dc.identifier.citation | Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. 2010, 123 (Pt 24):4280-91 J. Cell. Sci. | en |
dc.identifier.issn | 1477-9137 | |
dc.identifier.pmid | 21098633 | |
dc.identifier.doi | 10.1242/jcs.064006 | |
dc.identifier.uri | http://hdl.handle.net/10033/118568 | |
dc.description.abstract | Staphylococcus aureus, which is a leading cause of hospital-acquired infections, binds via fibronectin to integrin α5β1, a process that can promote host colonization in vivo. Integrin engagement induces actin cytoskeleton rearrangements that result in the uptake of S. aureus by non-professional phagocytic cells. Interestingly, we found that fibronectin-binding S. aureus trigger the redistribution of membrane microdomain components. In particular, ganglioside GM1 and GPI-linked proteins were recruited upon integrin β1 engagement, and disruption of membrane microdomains blocked bacterial internalization. Several membrane-microdomain-associated proteins, such as flotillin-1 and flotillin-2, as well as caveolin, were recruited to sites of bacterial attachment. Whereas dominant-negative versions of flotillin-2 did not affect bacterial attachment or internalization, cells deficient for caveolin-1 (Cav1(-/-)) showed increased uptake of S. aureus and other Fn-binding pathogens. Recruitment of membrane microdomains to cell-associated bacteria was unaltered in Cav1(-/-) cells. However, fluorescence recovery after photobleaching (FRAP) revealed an enhanced mobility of membrane-microdomain-associated proteins in the absence of caveolin-1. Enhanced membrane microdomain mobility and increased uptake of S. aureus was repressed by expression of wild-type caveolin-1, but not caveolin-1 G83S, which harbors a point mutation in the caveolin scaffolding domain. Similarly, chemical or physical stimulation of membrane fluidity led to increased uptake of S. aureus. These results highlight a crucial role for caveolin-1 in negative regulation of membrane microdomain mobility, thereby affecting endocytosis of bacteria-engaged integrins. This process might not only limit host cell invasion by integrin-binding bacterial pathogens, but might also be physiologically relevant for integrin-mediated cell adhesion. | |
dc.language.iso | en | en |
dc.title | Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. | en |
dc.type | Article | en |
dc.contributor.department | Lehrstuhl Zellbiologie X908, Universität Konstanz, Universitätsstr. 10, 78457 Konstanz, Germany. | en |
dc.identifier.journal | Journal of cell science | en |
refterms.dateFOA | 2011-12-15T00:00:00Z | |
html.description.abstract | Staphylococcus aureus, which is a leading cause of hospital-acquired infections, binds via fibronectin to integrin α5β1, a process that can promote host colonization in vivo. Integrin engagement induces actin cytoskeleton rearrangements that result in the uptake of S. aureus by non-professional phagocytic cells. Interestingly, we found that fibronectin-binding S. aureus trigger the redistribution of membrane microdomain components. In particular, ganglioside GM1 and GPI-linked proteins were recruited upon integrin β1 engagement, and disruption of membrane microdomains blocked bacterial internalization. Several membrane-microdomain-associated proteins, such as flotillin-1 and flotillin-2, as well as caveolin, were recruited to sites of bacterial attachment. Whereas dominant-negative versions of flotillin-2 did not affect bacterial attachment or internalization, cells deficient for caveolin-1 (Cav1(-/-)) showed increased uptake of S. aureus and other Fn-binding pathogens. Recruitment of membrane microdomains to cell-associated bacteria was unaltered in Cav1(-/-) cells. However, fluorescence recovery after photobleaching (FRAP) revealed an enhanced mobility of membrane-microdomain-associated proteins in the absence of caveolin-1. Enhanced membrane microdomain mobility and increased uptake of S. aureus was repressed by expression of wild-type caveolin-1, but not caveolin-1 G83S, which harbors a point mutation in the caveolin scaffolding domain. Similarly, chemical or physical stimulation of membrane fluidity led to increased uptake of S. aureus. These results highlight a crucial role for caveolin-1 in negative regulation of membrane microdomain mobility, thereby affecting endocytosis of bacteria-engaged integrins. This process might not only limit host cell invasion by integrin-binding bacterial pathogens, but might also be physiologically relevant for integrin-mediated cell adhesion. |
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