NDLI: Cdc42 and the Phosphatidylinositol 3-Kinase-Akt Pathway Are Essential for PspC-mediated Internalization of Pneumococci by Respiratory Epithelial Cells

Content Provider	Journal of Biological Chemistry (JBC)
Author	Agarwal, Vaibhav Hammerschmidt, Sven
Abstract	The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae, the cause of lobar pneumonia and invasive diseases. PspC interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor (pIgR) produced by respiratory epithelial cells. By adopting the retrograde machinery of human pIgR, this protein-protein interaction promotes colonization and transcytosis across the epithelial layer. Here, we explored the role of Rho family guanosine triphosphatases (GTPases), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) for ingestion of pneumococci via the human pIgR. Inhibition experiments suggested that the host-cell actin microfilaments and microtubules are essential for this pneumococcal uptake mechanism. By using specific GTPase-modifying toxins, inhibitors, and GTPase expression constructs we demonstrate that Cdc42, but not Rac1 and RhoA are involved in PspC-mediated invasion of pneumococci into host cells. Accordingly, Cdc42 is time-dependently activated during ingestion of pneumococci. In addition, PI3K and Akt are essential for ingestion of pneumococci by respiratory epithelial cells via the PspC-pIgR interaction. The subunit p85α of PI3K and Akt was activated during the infection process. Moreover, Akt activation upon pneumococcal invasion depends on PI3K. In conclusion, our results illustrate for the first time key signaling molecules of host cells that are required for PspC-pIgR-mediated invasion of pneumococci into epithelial cells. This unique and specific bacterial entry process is dependent on the cooperation and activation of Rho family GTPase Cdc42, PI3K, and Akt.
Related Links	http://www.jbc.org/content/284/29/19427.abstract
Ending Page	19436
Starting Page	19427
Page Count	10
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	29
Volume Number	284
DOI	10.1074/jbc.M109.003442
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2009-07-17
Access Restriction	Open
Subject Keyword	Mechanisms of Signal Transduction
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Cdc42 and the Phosphatidylinositol 3-Kinase-Akt Pathway Are Essential for PspC-mediated Internalization of Pneumococci by Respiratory Epithelial Cells*

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