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PMID: 12356723 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology.

The EMBO journal ·Vol. 21 ·No. 19 ·2002-10-01 ·Pages 5069-78

Niebuhr K, Giuriato S, Pedron T, Philpott DJ, Gaits F, Sable J, Sheetz MP, Parsot C, Sansonetti PJ, Payrastre B

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.

MeSH Terms
3T3 Cells Animals Bacterial Proteins/metabolism Cell Adhesion Enzyme Activation HeLa Cells Humans Kinetics Mice Mutagenesis, Site-Directed Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphatidylinositol Phosphates/metabolism Phosphoric Monoester Hydrolases/metabolism Polymerase Chain Reaction Recombinant Fusion Proteins/metabolism Shigella flexneri/enzymology Transfection
Chemicals
Bacterial Proteins Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositol Phosphates Recombinant Fusion Proteins phosphatidylinositol 5-phosphate Phosphatidylinositol 3-Kinases IpgD protein, Shigella flexneri Phosphoric Monoester Hydrolases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Niebuhr Kirsten
Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France.
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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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2002-10-01
Pages
5069-78
Language
English
Region
England
NLM ID
8208664
PMCID
PMC129044
Subset
IM
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