Integrin-linked kinase is required for vitronectin-mediated internalization ofStreptococcus pneumoniaeby host cells
Open Access
- 15 January 2009
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 122 (2), 256-267
- https://doi.org/10.1242/jcs.035600
Abstract
By interacting with components of the human host, including extracellular matrix (ECM) proteins, Streptococcus pneumoniae has evolved various strategies for colonization. Here, we characterized the interaction of pneumococci with the adhesive glycoprotein vitronectin and the contribution of this protein to pneumococcal uptake by host cells in an integrin-dependent manner. Specific interaction of S. pneumoniae with the heparin-binding sites of purified multimeric vitronectin was demonstrated by flow cytometry analysis. Host-cell-bound vitronectin promoted pneumococcal adherence to and invasion into human epithelial and endothelial cells. Pneumococci were trapped by microspike-like structures, which were induced upon contact of pneumococci with host-cell-bound vitronectin. αvβ3 integrin was identified as the major cellular receptor for vitronectin-mediated adherence and uptake of pneumococci. Ingestion of pneumococci by host cells via vitronectin required a dynamic actin cytoskeleton and was dependent on integrin-linked kinase (ILK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), as demonstrated by gene silencing or in inhibition experiments. In conclusion, pneumococci exploit the vitronectin–αvβ3-integrin complex as a cellular receptor for invasion and this integrin-mediated internalization requires the cooperation between the host signalling molecules ILK, PI3K and Akt.Keywords
This publication has 71 references indexed in Scilit:
- Integrin-linked kinase is required for epidermal and hair follicle morphogenesisThe Journal of cell biology, 2007
- Versatility of pneumococcal surface proteinsMicrobiology, 2006
- 'Small' talk: Opa proteins as mediators of Neisseria–host-cell communicationCurrent Opinion in Microbiology, 2003
- IntegrinsCell, 2002
- Molecular Dissection of Actopaxin-Integrin-linked Kinase-Paxillin Interactions and Their Role in Subcellular LocalizationJournal of Biological Chemistry, 2002
- A Novel Integrin-Linked Kinase–Binding Protein, Affixin, Is Involved in the Early Stage of Cell–Substrate InteractionThe Journal of cell biology, 2001
- Vitronectin‐dependent invasion of epithelial cells by Neisseria gonorrhoeae involves αv integrin receptorsFEBS Letters, 1998
- Isolation and characterisation of a vitronectin-binding surface protein from Staphylococcus aureusBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1995
- Binding of Laminin, Type IV Collagen, and Vitronectin by Streptococcus PneumoniaeZentralblatt für Bakteriologie, 1992
- Vitronectin-Binding Surface Proteins of Staphylococcus AureusZentralblatt für Bakteriologie, 1992