Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens.

2.50
Hdl Handle:
http://hdl.handle.net/10033/118568
Title:
Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens.
Authors:
Hoffmann, Christine; Berking, Anne; Agerer, Franziska; Buntru, Alexander; Neske, Florian; Chhatwal, G Singh; Ohlsen, Knut; Hauck, Christof R
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.
Affiliation:
Lehrstuhl Zellbiologie X908, Universität Konstanz, Universitätsstr. 10, 78457 Konstanz, Germany.
Citation:
Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. 2010, 123 (Pt 24):4280-91 J. Cell. Sci.
Journal:
Journal of cell science
Issue Date:
15-Dec-2010
URI:
http://hdl.handle.net/10033/118568
DOI:
10.1242/jcs.064006
PubMed ID:
21098633
Type:
Article
Language:
en
ISSN:
1477-9137
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorHoffmann, Christineen
dc.contributor.authorBerking, Anneen
dc.contributor.authorAgerer, Franziskaen
dc.contributor.authorBuntru, Alexanderen
dc.contributor.authorNeske, Florianen
dc.contributor.authorChhatwal, G Singhen
dc.contributor.authorOhlsen, Knuten
dc.contributor.authorHauck, Christof Ren
dc.date.accessioned2011-01-04T15:30:24Z-
dc.date.available2011-01-04T15:30:24Z-
dc.date.issued2010-12-15-
dc.identifier.citationCaveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. 2010, 123 (Pt 24):4280-91 J. Cell. Sci.en
dc.identifier.issn1477-9137-
dc.identifier.pmid21098633-
dc.identifier.doi10.1242/jcs.064006-
dc.identifier.urihttp://hdl.handle.net/10033/118568-
dc.description.abstractStaphylococcus 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.en
dc.language.isoenen
dc.titleCaveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens.en
dc.typeArticleen
dc.contributor.departmentLehrstuhl Zellbiologie X908, Universität Konstanz, Universitätsstr. 10, 78457 Konstanz, Germany.en
dc.identifier.journalJournal of cell scienceen

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