Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology |
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Authors: | Niebuhr Kirsten Giuriato Sylvie Pedron Thierry Philpott Dana J Gaits Frédérique Sable Julia Sheetz Michael P Parsot Claude Sansonetti Philippe J Payrastre Bernard |
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Institution: | Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France. |
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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)P(2)] into phosphatidylinositol 5-monophosphate PtdIns(5)P] that then accumulates. Transfection experiments indicate that the transformation of PtdIns(4,5)P(2) 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. |
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