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Conversion of PtdIns(4,5)P2 into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology

Kirsten Niebuhr, Sylvie Giuriato, Thierry Pedron, Dana J. Philpott, Frédérique Gaits, Julia Sable, Michael P. Sheetz, Claude Parsot, Philippe J. Sansonetti, Bernard Payrastre

Author Affiliations

  1. Kirsten Niebuhr1,
  2. Sylvie Giuriato2,
  3. Thierry Pedron1,
  4. Dana J. Philpott1,
  5. Frédérique Gaits2,
  6. Julia Sable3,
  7. Michael P. Sheetz3,
  8. Claude Parsot1,
  9. Philippe J. Sansonetti1 and
  10. Bernard Payrastre*,2
  1. 1 Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724, Paris, cedex 15, France
  2. 2 INSERM, Unité 563, Centre de Physiopathologie Toulouse Purpan, Departement d'Oncogenèse et signalisation dans les cellules haematopoïetiques, IFR 30, Hôpital Purpan, 31059, Toulouse, cedex, France
  3. 3 Department of Biological Sciences, PO Box 2408, Columbia University, Sherman Fairchild Center, 1212 Amsterdam Avenue, New York, NY, 10027, USA
  1. *Corresponding author. E-mail: payrastr{at}toulouse.inserm.fr
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Abstract

Phosphoinositides play a central role in the control of several cellular events including actin cytoskeleton organization. Here we show that, upon infection of epithelial cells with the Gram‐negative pathogen Shigella flexneri, the virulence factor IpgD is translocated directly into eukaryotic cells and acts as a potent inositol 4‐phosphatase that specifically dephosphorylates phosphatidylinositol 4,5‐bisphosphate [PtdIns(4,5)P2] into phosphatidylinositol 5‐monophosphate [PtdIns(5)P] that then accumulates. Transfection experiments indicate that the transformation of PtdIns(4,5)P2 into PtdIns(5)P by IpgD is responsible for dramatic morphological changes of the host cell, leading to a decrease in membrane tether force associated with membrane blebbing and actin filament remodelling. These data provide the molecular basis for a new mechanism employed by a pathogenic bacterium to promote membrane ruffling at the entry site.

  • Received June 5, 2002.
  • Revision received August 6, 2002.
  • Accepted August 12, 2002.
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