Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa.

Abstract

Pseudomonas aeruginosa has the capacity to invade lung epithelial cells by co-opting the intrinsic endocytic properties of lipid rafts, which are rich in cholesterol, sphingolipids, and proteins, such as caveolin-1 and -2. We compared intratracheal Pseudomonas infection in wild type and caveolin-deficient mice to investigate the role of caveolin proteins in the pathogenesis of Pseudomonas pneumonia. Unlike wild type mice, which succumb to pneumonia, caveolin-deficient mice are resistant to Pseudomonas. We observed that Pseudomonas invasion of lung epithelial cells is dependent on caveolin-2 but not caveolin-1. Phosphorylation of caveolin-2 by Src family kinases is an essential event for Pseudomonas invasion. Our studies also reveal the existence of a distinct signaling mechanism in lung epithelial cells mediated by COOH-terminal Src kinase (Csk) that negatively regulates Pseudomonas invasion. Csk migrates to lipid raft domains, where it decreases phosphorylation of caveolin-2 by inactivating c-Src. Whereas Pseudomonas co-opts the endocytic properties of caveolin-2 for invasion, there also exists in these cells an intrinsic Csk-dependent cellular defense mechanism aimed at impairing this activity. The success of Pseudomonas in co-opting lipid raft-mediated endocytosis to invade lung epithelial cells may depend on the relative strengths of these counteracting signaling activities.

• Authors: David W Zaas, Zachary D Swan, Bethany J Brown, Guojie Li, Scott H Randell, Simone Degan, Mary E Sunday, Jo Rae Wright, Soman N Abraham
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 15 Pg. 9955-64 (Apr 10 2009) ISSN: 0021-9258 [Print] United States
• PMID: 19211560 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Caveolins
• Protein-Tyrosine Kinases
• CSK Tyrosine-Protein Kinase
• src-Family Kinases

Topics

• Animals
• CSK Tyrosine-Protein Kinase
• Caveolins (metabolism)
• Cell Movement
• Endocytosis
• Epithelial Cells (microbiology)
• Lung (microbiology)
• Membrane Microdomains (metabolism)
• Mice
• Mice, Knockout
• Microscopy, Confocal
• Protein Structure, Tertiary
• Protein-Tyrosine Kinases (metabolism)
• Pseudomonas Infections (metabolism)
• Pseudomonas aeruginosa (metabolism)
• Time Factors
• src-Family Kinases