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J Cell Sci. 2016 Aug 1;129(15):2937-49. doi: 10.1242/jcs.186213. Epub 2016 Jun 16.

Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells.

Author information

1
Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
2
Institute of Biological and Medical Imaging (IBMI), Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany Institute for Biological Imaging, Technical University of Munich, Arcisstrasse 21, Munich 80333, Germany.
3
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
4
Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
5
Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany m.aepfelbacher@uke.de.

Abstract

Activation and invasion of the vascular endothelium by Staphylococcus aureus is a major cause of sepsis and endocarditis. For endothelial cell invasion, S. aureus triggers actin polymerization through Cdc42, N-WASp (also known as WASL) and the Arp2/3 complex to assemble a phagocytic cup-like structure. Here, we show that after stimulating actin polymerization staphylococci recruit Cdc42GAP (also known as ARHGAP1) 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 the exocyst complex. When Cdc42GAP recruitment by staphylococci was prevented by blocking recycling endocytic vesicles or the 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. Analogous mechanisms might govern other Cdc42-dependent cell functions.

KEYWORDS:

Cdc42GAP; Endothelium; Phagocytosis; Recycling endosomes; Staphylococci

PMID:
27311480
PMCID:
PMC5004874
DOI:
10.1242/jcs.186213
[Indexed for MEDLINE]
Free PMC Article

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