The secreted Salmonella dublin phosphoinositide phosphatase, SopB, localizes to PtdIns(3)P-containing endosomes and perturbs normal endosome to lysosome trafficking.
Invasion and survival in mammalian cells by Salmonella enterica is mediated by bacterial proteins that are delivered to the host cell cytoplasm by type III secretion systems. One of these proteins, SopB/SigD, is a phosphoinositide phosphatase that can hydrolyse a number of substrates in vitro including PtdIns(3,5)P2. These substrates are, however, likely to be restricted in vivo by the localization of SopB, as different phosphoinositides have distinct spatial distributions in mammalian cells. In the present study, we show that heterologously expressed SopB localizes almost exclusively to endosomes containing the lipid PtdIns(3)P, and on which ESCRT (endosomal sorting complexes required for transport) proteins assemble. Furthermore, we present evidence that SopB can inhibit trafficking of activated epidermal growth factor receptor to the lysosome. These results provide further evidence that PtdIns(3,5)P2, a lipid involved in endosomal maturation, may be a relevant in vivo substrate of SopB. We hypothesize that reduction of PtdIns(3,5)P2 levels in cells by the action of SopB may perturb the function of a subset of ESCRT proteins that have previously been shown to bind to this lipid.
Dukes
Joseph D
JD
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Lee
Huailo
H
Hagen
Rachel
R
Reaves
Barbara J
BJ
Layton
Abigail N
AN
Galyov
Edouard E
EE
Whitley
Paul
P
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism; D012475:Salmonella / Q000201:enzymology*
D001426:Bacterial Proteins; D018129:Phosphatidylinositol Phosphates; D011956:Receptors, Cell Surface; C060974:phosphatidylinositol 3,4,5-triphosphate; C489224:SopB protein, Salmonella