Biochem. J. (2006) 395
(239–247) (Printed in Great Britain)
The secreted Salmonella dublin phosphoinositide phosphatase, SopB, localizes to PtdIns(3)P-containing endosomes and perturbs normal endosome to lysosome trafficking
Joseph D. DUKES*, Huailo LEE*, Rachel HAGEN*, Barbara J. REAVES*, Abigail N. LAYTON†, Edouard E. GALYOV† and Paul WHITLEY*1
*Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U.K., and †Institute for Animal Health, Compton, Berkshire RG20 7NN, U.K.
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.
Key words: endosome, endosomal sorting complexes required for transport (ESCRT), lysosome trafficking, PtdIns(3,5)P2, Salmonella dublin, SopB.
Abbreviations used: MVB, multivesicular body; CHMP, charged MVB protein; CHO, Chinese-hamster ovary; CI-M6PR, cation independent mannose 6-phosphate receptor; DMEM, Dulbecco's modified minimal essential medium; EEA1, early endosome antigen 1; EGF, epidermal growth factor; EGFR, EGF receptor; ESCRT, endosomal sorting complexes required for transport; FENS-1, FYVE domain containing protein localized to endosomes-1; GFP, green fluorescent protein; NCS, newborn calf serum; PI3K, phosphoinositide 3-kinase; PIKfyve, PhosphoInositide Kinase for five position containing a Fyve finger domain; SCV, Salmonella-containing vacuole; SPI, Salmonella pathogenicity island; TGN, trans-Golgi network; TTSS, type III secretion system; Vps, vacuolar protein sorting; wt, wild-type.
1To whom correspondence should be addressed (email bssprw@bath.ac.uk).
Received 1 September 2005/16 December 2005; accepted 6 January 2006
Published as BJ Immediate Publication 6 January 2006, doi:10.1042/BJ20051451
The Biochemical Society, London ©2006
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