Fuchs, Evelyn, Hass, Alexander K., Spooner, Robert A. , Yoshimura, Shin-ichiro , Lord, Mike (J. Mike) and Barr, Francis A.. (2007) Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. Journal of Cell Biology, Vol.177 (No.6). pp. 1133-1143. ISSN 0021-9525

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Abstract

Rab family guanosine triphosphatases (GTPases) together with their regulators define specific pathways of membrane traffic within eukaryotic cells. In this study, we have investigated which Rab GTPase-activating proteins (GAPs) can interfere with the trafficking of Shiga toxin from the cell surface to the Golgi apparatus and studied transport of the epidermal growth factor (EGF) from the cell surface to endosomes. This screen identifies 6 (EVI5, RN-tre/USP6NL, TBC1D10A–C, and TBC1D17) of 39 predicted human Rab GAPs as specific regulators of Shiga toxin but not EGF uptake. We show that Rab43 is the target of RN-tre and is required for Shiga toxin uptake. In contrast, RabGAP-5, a Rab5 GAP, was unique among the GAPs tested and reduced the uptake of EGF but not Shiga toxin. These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Guanosine triphosphate, Eucaryotic cells
Journal or Publication Title:	Journal of Cell Biology
Publisher:	Rockefeller University Press
ISSN:	0021-9525
Date:	11 June 2007
Volume:	Vol.177
Number:	No.6
Page Range:	pp. 1133-1143
Identification Number:	10.1083/jcb.200612068
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Max-Planck-Gesellschaft zur Förderung der Wissenschaften [Max Planck Society for the Advancement of Science], Deutsche Forschungsgemeinschaft (DFG), National Institutes of Health (U.S.) (NIH)
Grant number:	5 U01AI 65869 (National Institutes of Health)
References:	Ahmadian, M.R., P. Stege, K. Scheffzek, and A. Wittinghofer. 1997. Confi rmation of the arginine-fi nger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nat. Struct. Biol. 4:686–689. Albert, S., and D. Gallwitz. 1999. Two new members of a family of Ypt/Rab GTPase activating proteins. Promiscuity of substrate recognition. J. Biol. Chem. 274:33186–33189. Albert, S., E. Will, and D. Gallwitz. 1999. Identifi cation of the catalytic domains and their functionally critical arginine residues of two yeast GTPaseactivating proteins specifi c for Ypt/Rab transport GTPases. EMBO J. 18:5216–5225. Bonifacino, J.S., and R. Rojas. 2006. Retrograde transport from endosomes to the trans-Golgi network. Nat. Rev. Mol. Cell Biol. 7:568–579. Choudhury, R., A. Diao, F. Zhang, E. Eisenberg, A. Saint-Pol, C. Williams, A. Konstantakopoulos, J. Lucocq, L. Johannes, C. Rabouille, et al. 2005. Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein traffi cking between endosomes and the trans-Golgi network. Mol. Biol. Cell. 16:3467–3479. Cuif, M.H., F. Possmayer, H. Zander, N. Bordes, F. Jollivet, A. Couedel- Courteille, I. Janoueix-Lerosey, G. Langsley, M. Bornens, and B. Goud. 1999. Characterization of GAPCenA, a GTPase activating protein for Rab6, part of which associates with the centrosome. EMBO J. 18:1772–1782. Del Nery, E., S. Miserey-Lenkei, T. Falguieres, C. Nizak, L. Johannes, F. Perez, and B. Goud. 2006. Rab6A and Rab6A’ GTPases play non-overlapping roles in membrane traffi cking. Traffi c. 7:394–407. Du, L.L., and P. Novick. 2001. Purifi cation and properties of a GTPase-activating protein for yeast Rab GTPases. Methods Enzymol. 329:91–99. Girod, A., B. Storrie, J.C. Simpson, L. Johannes, B. Goud, L.M. Roberts, J.M. Lord, T. Nilsson, and R. Pepperkok. 1999. Evidence for a COP-Iindependent transport route from the Golgi complex to the endoplasmic reticulum. Nat. Cell Biol. 1:423–430. Haas, A.K., E. Fuchs, R. Kopajtich, and F.A. Barr. 2005. A GTPase-activating protein controls Rab5 function in endocytic traffi cking. Nat. Cell Biol. 7:887–893. Hyvola, N., A. Diao, E. McKenzie, A. Skippen, S. Cockcroft, and M. Lowe. 2006. Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. EMBO J. 25:3750–3761. Johannes, L., and B. Goud. 1998. Surfi ng on a retrograde wave: how does Shiga toxin reach the endoplasmic reticulum? Trends Cell Biol. 8:158–162. Johannes, L., and B. Goud. 2000. Facing inward from compartment shores: how many pathways were we looking for? Traffi c. 1:119–123. Johannes, L., D. Tenza, C. Antony, and B. Goud. 1997. Retrograde transport of KDEL-bearing B-fragment of Shiga toxin. J. Biol. Chem. 272:19554–19561. Kupzig, S., D. Deaconescu, D. Bouyoucef, S.A. Walker, Q. Liu, C.L. Polte, O. Daumke, T. Ishizaki, P.J. Lockyer, A. Wittinghofer, and P.J. Cullen. 2006. GAP1 family members constitute bifunctional Ras and Rap GTPaseactivating proteins. J. Biol. Chem. 281:9891–9900. Lanzetti, L., V. Rybin, M.G. Malabarba, S. Christoforidis, G. Scita, M. Zerial, and P.P. Di Fiore. 2000. The Eps8 protein coordinates EGF receptor signalling through Rac and traffi cking through Rab5. Nature. 408:374–377. Lauvrak, S.U., M.L. Torgersen, and K. Sandvig. 2004. Effi cient endosome-to- Golgi transport of Shiga toxin is dependent on dynamin and clathrin. J. Cell Sci. 117:2321–2331. Lu, L., G. Tai, and W. Hong. 2004. Autoantigen Golgin-97, an effector of Arl1 GTPase, participates in traffi c from the endosome to the trans-golgi network. Mol. Biol. Cell. 15:4426–4443. Mallard, F., C. Antony, D. Tenza, J. Salamero, B. Goud, and L. Johannes. 1998. Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of shiga toxin B-fragment transport. J. Cell Biol. 143:973–990. Mallard, F., B.L. Tang, T. Galli, D. Tenza, A. Saint-Pol, X. Yue, C. Antony, W. Hong, B. Goud, and L. Johannes. 2002. Early/recycling endosomes-to- TGN transport involves two SNARE complexes and a Rab6 isoform. J. Cell Biol. 156:653–664. Matanis, T., A. Akhmanova, P. Wulf, E. Del Nery, T. Weide, T. Stepanova, N. Galjart, F. Grosveld, B. Goud, C.I. De Zeeuw, et al. 2002. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dyneindynactin motor complex. Nat. Cell Biol. 4:986–992. Monier, S., F. Jollivet, I. Janoueix-Lerosey, L. Johannes, and B. Goud. 2002. Characterization of novel Rab6-interacting proteins involved in endosometo- TGN transport. Traffi c. 3:289–297. Munro, S. 2002. Organelle identity and the targeting of peripheral membrane proteins. Curr. Opin. Cell Biol. 14:506–514. Nichols, B.J., A.K. Kenworthy, R.S. Polishchuk, R. Lodge, T.H. Roberts, K. Hirschberg, R.D. Phair, and J. Lippincott-Schwartz. 2001. Rapid cycling of lipid raft markers between the cell surface and Golgi complex. J. Cell Biol. 153:529–541. Niyogi, S.K. 2005. Shigellosis. J. Microbiol. 43:133–143. O’Loughlin, E.V., and R.M. Robins-Browne. 2001. Effect of Shiga toxin and Shiga-like toxins on eukaryotic cells. Microbes Infect. 3:493–507. Pan, X., S. Eathiraj, M. Munson, and D.G. Lambright. 2006. TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-fi nger mechanism. Nature. 442:303–306. Pereira, G., T.U. Tanaka, K. Nasmyth, and E. Schiebel. 2001. Modes of spindle pole body inheritance and segregation of the Bfa1p-Bub2p checkpoint protein complex. EMBO J. 20:6359–6370. Pfeffer, S.R. 2001. Rab GTPases: specifying and deciphering organelle identity and function. Trends Cell Biol. 11:487–491. Rak, A., R. Fedorov, K. Alexandrov, S. Albert, R.S. Goody, D. Gallwitz, and A.J. Scheidig. 2000. Crystal structure of the GAP domain of Gyp1p: fi rst insights into interaction with Ypt/Rab proteins. EMBO J. 19:5105–5113. Sandvig, K., and B. van Deurs. 2002. Membrane traffi c exploited by protein toxins. Annu. Rev. Cell Dev. Biol. 18:1–24. Sandvig, K., S. Olsnes, J.E. Brown, O.W. Petersen, and B. van Deurs. 1989. Endocytosis from coated pits of Shiga toxin: a glycolipid-binding protein from Shigella dysenteriae 1. J. Cell Biol. 108:1331–1343. Sandvig, K., O. Garred, K. Prydz, J.V. Kozlov, S.H. Hansen, and B. van Deurs. 1992. Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. Nature. 358:510–512. Short, B., C. Preisinger, J. Schaletzky, R. Kopajtich, and F.A. Barr. 2002. The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Curr. Biol. 12:1792–1795. Sigismund, S., T. Woelk, C. Puri, E. Maspero, C. Tacchetti, P. Transidico, P.P. Di Fiore, and S. Polo. 2005. Clathrin-independent endocytosis of ubiquitinated cargos. Proc. Natl. Acad. Sci. USA. 102:2760–2765. Sohda, M., Y. Misumi, S. Yoshimura, N. Nakamura, T. Fusano, S. Sakisaka, S. Ogata, J. Fujimoto, N. Kiyokawa, and Y. Ikehara. 2005. Depletion of vesicle-tethering factor p115 causes mini-stacked Golgi fragments with delayed protein transport. Biochem. Biophys. Res. Commun. 338:1268–1274. Spooner, R.A., P.D. Watson, C.J. Marsden, D.C. Smith, K.A. Moore, J.P. Cook, J.M. Lord, and L.M. Roberts. 2004. Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. Biochem. J. 383:285–293. Spooner, R.A., D.C. Smith, A.J. Easton, L.M. Roberts, and J.M. Lord. 2006. Retrograde transport pathways utilised by viruses and protein toxins. Virol. J. 3:26. Stenmark, H., R.G. Parton, O. Steele-Mortimer, A. Lutcke, J. Gruenberg, and M. Zerial. 1994. Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J. 13:1287–1296. Strom, M., P. Vollmer, T.J. Tan, and D. Gallwitz. 1993. A yeast GTPase-activating protein that interacts specifi cally with a member of the Ypt/Rab family. Nature. 361:736–739. Tai, G., L. Lu, T.L. Wang, B.L. Tang, B. Goud, L. Johannes, and W. Hong. 2004. Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex in transport from the early/recycling endosome to the trans-Golgi network. Mol. Biol. Cell. 15:4011–4022. White, J., L. Johannes, F. Mallard, A. Girod, S. Grill, S. Reinsch, P. Keller, B. Tzschaschel, A. Echard, B. Goud, and E.H. Stelzer. 1999. Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells. J. Cell Biol. 147:743–760. Zerial, M., and H. McBride. 2001. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2:107–117.
URI:	http://wrap.warwick.ac.uk/id/eprint/408

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