Rauch, L.* ; Hennings, K.* ; Trasak, C.* ; Röder, A.* ; Schröder, B. ; Koch-Nolte, F.* ; Rivera-Molina, F.* ; Toomre, D.* ; Aepfelbacher, M.*
     
    
        
Staphylococcus aureus recruits Cdc42GAP via recycling endosomes and exocyst to invade human endothelial cells.
    
    
        
    
    
        
        J. Cell Sci. 129, 2937-2949 (2016)
    
    
    
      
      
	
	    Activation and invasion of the vascular endothelium by Staphylococcus aureus (S. aureus) is a major cause of sepsis and endocarditis. For endothelial cell invasion, S. aureus triggers actin polymerization via Cdc42, N-WASp and Arp2/3 complex to assemble a phagocytic cup-like structure. Here we show that after stimulating actin polymerization staphylococci recruit Cdc42GAP which deactivates Cdc42 and terminates actin polymerization in the phagocytic cups. Cdc42GAP is delivered to the invading bacteria on recycling endocytic vesicles in concert with exocyst complex. When Cdc42GAP recruitment by staphylococci was prevented by blocking recycling endocytic vesicles or exocyst complex or when Cdc42 was constitutively activated, phagocytic cup closure was impaired and endothelial cell invasion was inhibited. Thus, to complete invasion of the endothelium staphylococci reorient recycling endocytic vesicles to recruit Cdc42GAP which terminates Cdc42-induced actin polymerization in phagocytic cups. Analogical mechanisms may govern other Cdc42-dependent cell functions.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
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        Keywords
        Cdc42gap ; Phagocytosis ; Staphylococci ; Endothelium ; Recycling Endosomes; Gtpase-activating Proteins; F-actin; Rho Gtpases; Phagocytosis; Complex; Binding; Polarity; Identification; Expression; Maturation
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2016
    
 
    
        Prepublished in Year
        
    
 
    
        HGF-reported in Year
        2016
    
 
    
    
        ISSN (print) / ISBN
        0021-9533
    
 
    
        e-ISSN
        1477-9137
    
 
    
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	    Volume: 129,  
	    Issue: 15,  
	    Pages: 2937-2949 
	    Article Number: ,  
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            Company of Biologists
        
 
        
            Publishing Place
            Cambridge
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30205 - Bioengineering and Digital Health
    
 
    
        Research field(s)
        Enabling and Novel Technologies
    
 
    
        PSP Element(s)
        G-505500-001
    
 
    
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        Erfassungsdatum
        2016-06-24