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Sci. Signal., 20 September 2011
Vol. 4, Issue 191, p. ra61
[DOI: 10.1126/scisignal.2001619]

RESEARCH ARTICLES

Shigella flexneri Infection Generates the Lipid PI5P to Alter Endocytosis and Prevent Termination of EGFR Signaling

Damien Ramel1, Frédéric Lagarrigue1, Véronique Pons1, Joëlle Mounier2, Sophie Dupuis-Coronas1, Gaëtan Chicanne1, Philippe J. Sansonetti2,3, Frédérique Gaits-Iacovoni1*, Hélène Tronchère1*, and Bernard Payrastre1*{dagger}

1 INSERM, U1048, Université Toulouse 3, I2MC and Hôpital de Toulouse, Avenue Jean Poulhès BP84225, 31432 Toulouse Cedex 04, France.
2 INSERM, U786, Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris, France.
3 Département de Microbiologie et Maladies Infectieuses, Collège de France, 75005 Paris, France.

* These authors contributed equally to this work.

Abstract: The phosphoinositide metabolic pathway, which regulates cellular processes implicated in survival, motility, and trafficking, is often subverted by bacterial pathogens. Shigella flexneri, a bacterium that causes dysentery, injects IpgD, a phosphoinositide phosphatase that generates the lipid phosphatidylinositol 5-phosphate (PI5P), into host cells, thereby activating the phosphoinositide 3-kinase–Akt survival pathway. We show that epidermal growth factor receptor (EGFR) is required for PI5P-dependent activation of Akt in infected HeLa cells or cells ectopically expressing IpgD. Cells treated with PI5P had increased numbers of early endosomes with activated EGFR, no detectable EGFR in the late endosomal or lysosomal compartments, and prolonged EGFR signaling. Endosomal recycling and retrograde pathways were spared, indicating that the effect of PI5P on the degradative route to the late endocytic compartments was specific. Thus, we identified PI5P, which was enriched in endosomes, as a regulator of vesicular trafficking that alters growth factor receptor signaling by impairing lysosomal degradation, a property used by S. flexneri to favor survival of host cells.

{dagger} To whom correspondence should be addressed. E-mail: bernard.payrastre{at}inserm.fr

Citation: D. Ramel, F. Lagarrigue, V. Pons, J. Mounier, S. Dupuis-Coronas, G. Chicanne, P. J. Sansonetti, F. Gaits-Iacovoni, H. Tronchère, B. Payrastre, Shigella flexneri Infection Generates the Lipid PI5P to Alter Endocytosis and Prevent Termination of EGFR Signaling. Sci. Signal. 4, ra61 (2011).

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