SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34.

Mallo GV, Espina M, Smith AC, Terebiznik MR, Alemán A, Finlay BB, Rameh LE, Grinstein S, Brumell JH
J Cell Biol. 2008 182 (4): 741-52

PMID: 18725540 · PMCID: PMC2518712 · DOI:10.1083/jcb.200804131

Salmonella colonizes a vacuolar niche in host cells during infection. Maturation of the Salmonella-containing vacuole (SCV) involves the formation of phosphatidylinositol 3-phosphate (PI(3)P) on its outer leaflet. SopB, a bacterial virulence factor with phosphoinositide phosphatase activity, was proposed to generate PI(3)P by dephosphorylating PI(3,4)P2, PI(3,5)P2, and PI(3,4,5)P3. Here, we examine the mechanism of PI(3)P formation during Salmonella infection. SopB is required to form PI(3,4)P2/PI(3,4,5)P3 at invasion ruffles and PI(3)P on nascent SCVs. However, we uncouple these events experimentally and reveal that SopB does not dephosphorylate PI(3,4)P2/PI(3,4,5)P3 to produce PI(3)P. Instead, the phosphatase activity of SopB is required for Rab5 recruitment to the SCV. Vps34, a PI3-kinase that associates with active Rab5, is responsible for PI(3)P formation on SCVs. Therefore, SopB mediates PI(3)P production on the SCV indirectly through recruitment of Rab5 and its effector Vps34. These findings reveal a link between phosphoinositide phosphatase activity and the recruitment of Rab5 to phagosomes.

MeSH Terms (16)

Bacterial Proteins Biological Transport Cell Membrane Cell Surface Extensions Enzyme Activation HeLa Cells Humans Models, Biological Mutation Phosphatidylinositol 3-Kinases Phosphatidylinositol Phosphates Phosphoinositide-3 Kinase Inhibitors Protein Kinase Inhibitors rab5 GTP-Binding Proteins Salmonella Vacuoles

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