Rabenosyn-5, a Novel Rab5 Effector, Is Complexed with hVPS45 and Recruited to Endosomes through a FYVE Finger Domain

doi:10.1083/jcb.151.3.601

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Published online 30 October 2000. doi:10.1083/jcb.151.3.601

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© The Rockefeller University Press, 0021-9525/2000/10/601/ $5.00
The Journal of Cell Biology, Volume 151, Number 3, October 30, 2000 601-612

Original Article

Rabenosyn-5, a Novel Rab5 Effector, Is Complexed with hVPS45 and Recruited to Endosomes through a FYVE Finger Domain

Erik Nielsen^a, Savvas Christoforidis^a, Sandrine Uttenweiler-Joseph^b, Marta Miaczynska^a, Frederique Dewitte^c, Matthias Wilm^b, Bernard Hoflack^c, and Marino Zerial^a
^a Max-Planck-Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany
^b European Molecular Biology Laboratory, 69117 Heidelberg, Germany
^c Institut de Biologie de Lille, Centre National de la Recherche Scientifique EP 525/Institut Pasteur de Lille 1, 59021 Lille, France

Correspondence to: Marino Zerial, Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse, 01307 Dresden, Germany. Tel:49-6221-387-232 Fax:49-6221-387-512

Rab5 regulates endocytic membrane traffic by specifically recruitingcytosolic effector proteins to their site of action on earlyendosomal membranes. We have characterized a new Rab5 effectorcomplex involved in endosomal fusion events. This complex includesa novel protein, Rabenosyn-5, which, like the previously characterizedRab5 effector early endosome antigen 1 (EEA1), contains an FYVEfinger domain and is recruited in a phosphatidylinositol-3-kinase–dependentfashion to early endosomes. Rabenosyn-5 is complexed to theSec1-like protein hVPS45. hVPS45 does not interact directlywith Rab5, therefore Rabenosyn-5 serves as a molecular linkbetween hVPS45 and the Rab5 GTPase. This property suggests thatRabenosyn-5 is a closer mammalian functional homologue of yeastVac1p than EEA1. Furthermore, although both EEA1 and Rabenosyn-5are required for early endosomal fusion, only overexpressionof Rabenosyn-5 inhibits cathepsin D processing, suggesting thatthe two proteins play distinct roles in endosomal trafficking.We propose that Rab5-dependent formation of membrane domainsenriched in phosphatidylinositol-3-phosphate has evolved asa mechanism for the recruitment of multiple effector proteinsto mammalian early endosomes, and that these domains are multifunctional,depending on the differing activities of the effector proteinsrecruited.

Key Words: endocytosis, Rab5, hVPS45, EEA1, Rabenosyn-5

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Roth, M. G. (2004). Phosphoinositides in Constitutive Membrane Traffic. Physiol. Rev. 84: 699-730 [Abstract] [Full Text]
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Merithew, E., Stone, C., Eathiraj, S., Lambright, D. G. (2003). Determinants of Rab5 Interaction with the N Terminus of Early Endosome Antigen 1. J. Biol. Chem. 278: 8494-8500 [Abstract] [Full Text]
Wang, L., Merz, A. J., Collins, K. M., Wickner, W. (2003). Hierarchy of protein assembly at the vertex ring domain for yeast vacuole docking and fusion. JCB 160: 365-374 [Abstract] [Full Text]
Hayes, S., Chawla, A., Corvera, S. (2002). TGF{beta} receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. JCB 158: 1239-1249 [Abstract] [Full Text]
Gougeon, P.-Y., Prosser, D. C., Da-Silva, L. F., Ngsee, J. K. (2002). Disruption of Golgi Morphology and Trafficking in Cells Expressing Mutant Prenylated Rab Acceptor-1. J. Biol. Chem. 277: 36408-36414 [Abstract] [Full Text]
Harris, E., Cardelli, J. (2002). RabD, a Dictyostelium Rab14-related GTPase, regulates phagocytosis and homotypic phagosome and lysosome fusion. J. Cell Sci. 115: 3703-3713 [Abstract] [Full Text]
Hattula, K., Furuhjelm, J., Arffman, A., Peranen, J. (2002). A Rab8-specific GDP/GTP Exchange Factor Is Involved in Actin Remodeling and Polarized Membrane Transport. Mol. Biol. Cell 13: 3268-3280 [Abstract] [Full Text]
Strick, D. J., Francescutti, D. M., Zhao, Y., Elferink, L. A. (2002). Mammalian Suppressor of Sec4 Modulates the Inhibitory Effect of Rab15 during Early Endocytosis. J. Biol. Chem. 277: 32722-32729 [Abstract] [Full Text]
Panopoulou, E., Gillooly, D. J., Wrana, J. L., Zerial, M., Stenmark, H., Murphy, C., Fotsis, T. (2002). Early Endosomal Regulation of Smad-dependent Signaling in Endothelial Cells. J. Biol. Chem. 277: 18046-18052 [Abstract] [Full Text]
Boeddinghaus, C., Merz, A. J., Laage, R., Ungermann, C. (2002). A cycle of Vam7p release from and PtdIns 3-P-dependent rebinding to the yeast vacuole is required for homotypic vacuole fusion. JCB 157: 79-90 [Abstract] [Full Text]
Rosenfeld, J. L., Moore, R. H., Zimmer, K.-P., Alpizar-Foster, E., Dai, W., Zarka, M. N., Knoll, B. J. (2002). Lysosome proteins are redistributed during expression of a GTP-hydrolysis-defective rab5a. J. Cell Sci. 114: 4499-4508 [Abstract] [Full Text]
Saito, K., Murai, J., Kajiho, H., Kontani, K., Kurosu, H., Katada, T. (2002). A Novel Binding Protein Composed of Homophilic Tetramer Exhibits Unique Properties for the Small GTPase Rab5. J. Biol. Chem. 277: 3412-3418 [Abstract] [Full Text]
Whyte, J. R. C., Munro, S. (2002). Vesicle tethering complexes in membrane traffic. J. Cell Sci. 115: 2627-2637 [Abstract] [Full Text]
Kauppi, M., Simonsen, A., Bremnes, B., Vieira, A., Callaghan, J., Stenmark, H., Olkkonen, V. M. (2002). The small GTPase Rab22 interacts with EEA1 and controls endosomal membrane trafficking. J. Cell Sci. 115: 899-911 [Abstract] [Full Text]
Seet, L.-F., Hong, W. (2001). Endofin, an Endosomal FYVE Domain Protein. J. Biol. Chem. 276: 42445-42454 [Abstract] [Full Text]
Mari, M., Macia, E., Le Marchand-Brustel, Y., Cormont, M. (2001). Role of the FYVE Finger and the RUN Domain for the Subcellular Localization of Rabip4. J. Biol. Chem. 276: 42501-42508 [Abstract] [Full Text]
Segev, N. (2001). Ypt/Rab GTPases: Regulators of Protein Trafficking. Sci Signal 2001: re11-re11 [Abstract] [Full Text]
Fratti, R. A., Backer, J. M., Gruenberg, J., Corvera, S., Deretic, V. (2001). Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. JCB 154: 631-644 [Abstract] [Full Text]
Lippe, R., Miaczynska, M., Rybin, V., Runge, A., Zerial, M. (2001). Functional Synergy between Rab5 Effector Rabaptin-5 and Exchange Factor Rabex-5 When Physically Associated in a Complex. Mol. Biol. Cell 12: 2219-2228 [Abstract] [Full Text]
Wendler, F., Page, L., Urbe, S., Tooze, S. A. (2001). Homotypic Fusion of Immature Secretory Granules During Maturation Requires Syntaxin 6. Mol. Biol. Cell 12: 1699-1709 [Abstract] [Full Text]
Mills, I., Urbe, S, Clague, M. (2001). Relationships between EEA1 binding partners and their role in endosome fusion. J. Cell Sci. 114: 1959-1965 [Abstract]
Prada-Delgado, A., Carrasco-Marin, E., Bokoch, G. M., Alvarez-Dominguez, C. (2001). Interferon-gamma Listericidal Action Is Mediated by Novel Rab5a Functions at the Phagosomal Environment. J. Biol. Chem. 276: 19059-19065 [Abstract] [Full Text]
Shin, M. E., Ogburn, K. D., Varban, O. A., Gilbert, P. M., Burd, C. G. (2001). FYVE Domain Targets Pib1p Ubiquitin Ligase to Endosome and Vacuolar Membranes. J. Biol. Chem. 276: 41388-41393 [Abstract] [Full Text]
Futter, C.E., Collinson, L.M., Backer, J.M., Hopkins, C.R. (2001). Human VPS34 is required for internal vesicle formation within multivesicular endosomes. JCB 155: 1251-1264 [Abstract] [Full Text]