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Broberg, CA, Zhang, L, Gonzalez, H, Laskowski-Arce, MA and Orth, K (2010) A Vibrio effector protein is an inositol phosphatase and disrupts host cell membrane integrity. Science 329:1660-2


The marine bacterium Vibrio parahaemolyticus causes gastroenteritis in humans and encodes the type III effector protein VPA0450, which contributes to host cell death caused by autophagy, cell rounding, and cell lysis. We found that VPA0450 is an inositol polyphosphate 5-phosphatase that hydrolyzed the D5 phosphate from the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate. VPA0450 disrupted cytoskeletal binding sites on the inner surface of membranes of human cells and caused plasma membrane blebbing, which compromised membrane integrity and probably contributed to cell death by facilitating lysis. Thus, bacterial pathogens can disrupt adaptor protein-binding sites required for proper membrane and cytoskeleton dynamics by altering the homeostasis of membrane-bound inositol-signaling molecules.


PubMed Online version:10.1126/science.1192850


Actins/metabolism; Amino Acid Sequence; Autophagy; Bacterial Proteins/chemistry; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Binding Sites; Cell Membrane/physiology; Cell Membrane/ultrastructure; Cell Shape; Computational Biology; Cytoskeleton/physiology; Cytoskeleton/ultrastructure; HeLa Cells; Homeostasis; Humans; Molecular Sequence Data; Phosphatidylinositol 4,5-Diphosphate/metabolism; Phosphatidylinositols/metabolism; Phosphoric Monoester Hydrolases/chemistry; Phosphoric Monoester Hydrolases/genetics; Phosphoric Monoester Hydrolases/metabolism; Protein Interaction Domains and Motifs; Signal Transduction; Transfection; Vibrio parahaemolyticus/enzymology; Vibrio parahaemolyticus/pathogenicity



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


Contributes to

GO:0004445: inositol-polyphosphate 5-phosphatase activity



Figure 3 shows that the mutant phenotype was unable to hydrolyze phosphate off phosphatidylinositol 4,5-bisphosphate

CACAO 4474

See also


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