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

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

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

  1. Damien Ramel1,
  2. Frédéric Lagarrigue1,
  3. Véronique Pons1,
  4. Joëlle Mounier2,
  5. Sophie Dupuis-Coronas1,
  6. Gaëtan Chicanne1,
  7. Philippe J. Sansonetti2,3,
  8. Frédérique Gaits-Iacovoni1,*,
  9. Hélène Tronchère1,*, and
  10. Bernard Payrastre1,*,
  1. 1INSERM, U1048, Université Toulouse 3, I2MC and Hôpital de Toulouse, Avenue Jean Poulhès BP84225, 31432 Toulouse Cedex 04, France.
  2. 2INSERM, U786, Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris, France.
  3. 3Département de Microbiologie et Maladies Infectieuses, Collège de France, 75005 Paris, France.
  1. To whom correspondence should be addressed. E-mail: bernard.payrastre{at}inserm.fr
  • * 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.

Citation:

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

Shigella flexneri Regulation of ARF6 Activation during Bacterial Entry via an IpgD-Mediated Positive Feedback Loop
A. C. Garza-Mayers, K. A. Miller, B. C. Russo, D. V. Nagda, and M. B. Goldberg
mBio 6, e02584-14-e02584-14 (1 May 2015)

TOM1 is a PI5P effector involved in the regulation of endosomal maturation
F. Boal, R. Mansour, M. Gayral, E. Saland, G. Chicanne, J.-M. Xuereb, M. Marcellin, O. Burlet-Schiltz, P. J. Sansonetti, B. Payrastre et al.
J. Cell Sci. 128, 815-827 (15 February 2015)

LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation
X. Tan, Y. Sun, N. Thapa, Y. Liao, A. C. Hedman, and R. A. Anderson
EMBO J. 34, 475-490 (12 February 2015)

Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells
J. L. Roxas, K. Ryan, G. Vedantam, and V. K. Viswanathan
Am. J. Physiol. Gastrointest. Liver Physiol. 307, G374-G380 (1 August 2014)

Lipid Sorting and Multivesicular Endosome Biogenesis
C. Bissig, and J. Gruenberg
Cold Spring Harb. Perspect. Biol. 5, a016816-a016816 (1 October 2013)

Systems-Level Overview of Host Protein Phosphorylation During Shigella flexneri Infection Revealed by Phosphoproteomics
C. Schmutz, E. Ahrne, C. A. Kasper, T. Tschon, I. Sorg, R. F. Dreier, A. Schmidt, and C. Arrieumerlou
MCP 12, 2952-2968 (1 October 2013)

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
T. Balla, E. Ahrne, C. A. Kasper, T. Tschon, I. Sorg, R. F. Dreier, A. Schmidt, and C. Arrieumerlou
Physiol. Rev. 93, 1019-1137 (1 July 2013)

PtdIns5P is an oxidative stress-induced second messenger that regulates PKB activation
D. R. Jones, R. Foulger, W.-J. Keune, Y. Bultsma, and N. Divecha
FASEB J. 27, 1644-1656 (1 April 2013)

Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration
A. Oppelt, V. H. Lobert, K. Haglund, A. M. Mackey, L. E. Rameh, K. Liestol, K. Oliver Schink, N. Marie Pedersen, E. M. Wenzel, E. M. Haugsten et al.
EMBO Rep. 14, 57-64 (3 January 2013)

In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P
S. N. Zolov, D. Bridges, Y. Zhang, W.-W. Lee, E. Riehle, R. Verma, G. M. Lenk, K. Converso-Baran, T. Weide, R. L. Albin et al.
Proc. Natl. Acad. Sci. USA 109, 17472-17477 (23 October 2012)

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