Jean Gruenberg
Objectives
Publications (1996-2006)
The Group

Jean Gruenberg

Jean Gruenberg received a Ph.D. in biochemistry from the University of Geneva in 1980. He worked as a post-doctoral fellow in parasitology at the University of California in Riverside (UCR) until 1984 and in cell biology at the European Molecular Biology Laboratory (EMBL) in Heidelberg. In 1987, he became group leader in the Cell Biology Programme of EMBL. He moved to Geneva in 1993, as Professor of Biochemistry at the University.

Objectives

Over the past 30 years, much effort has been devoted to the description of organelles, and then to the pathways followed by cargo proteins during secretion or endocytosis. Many key processes have been dissected at the molecular, and sometimes atomic, level, the current challenges being first to understand how molecular machines regulate each trafficking step and then how these different mechanisms are integrated. However, the principles that guide the movement of proteins and lipids and the specific organization of each compartment are still poorly understood: how is the linear organization of the genome translated into 3D cellular architecture?

Endosomes play a central role in the vacuolar apparatus of animal cells, at the crossroad between reutilization of components via recycling pathways or degradation in lysosomes. Understanding their functions, organization, and dynamics will contribute to elucidate fundamental cellular processes involved in nutrient uptake, immunity, signaling, adhesion, cellular membrane turnover and defense against toxins and pathogens. Our work has uncovered some of the principles responsible for the biogenesis and dynamic properties of endosomes, including specialized protein–lipid domains that are altered in some human pathologies. Using in vivo and in vitro strategies, we wish to characterize components, molecular assemblies and membrane domains that regulate the organization, dynamics and functions of endosomal membranes.

The figure below shows (protein-free) liposomes (0.7µm diamter) that spontaneously become multivesicular when they contain the correct isoform of the late endosomal lipid lysobisphosphatidic acid (2,2’-dioleoyl LBPA) and when their lumen is acidified to the pH of late endosomes (Matsuo et al. 2004. Sciences 303, 531-4). The liposomes are labeled with a fluorescent dye and visualized by fluorescence microscopy.

These multivesicular liposomes resemble the multivesicular late endosomes (figure below; immunogold-labeling of cryosections with anti-LBPA antibodies; gold: 10nm), where LBPA is found in vivo (Kobayashi et al., 1998. Nature 392, 193-7)

Publications (1996-2006)

Aniento, F., Gu, F., Parton, R. G. and Gruenberg, J. (1996). An endosomal beta COP is involved in the pH-dependent formation of transport vesicles destined for late endosomes. J Cell Biol 133, 29-41.

Huber, L. A., Pasquali, C., Gagescu, R., Zuk, A., Gruenberg, J. and Matlin, K. S. (1996). Endosomal fractions from viral K-ras-transformed MDCK cells reveal transformation specific changes on two-dimensional gel maps. Electrophoresis 17, 1734-40.

Gu, F., Aniento, F., Parton, R. G. and Gruenberg, J. (1997). Functional dissection of COP-I subunits in the biogenesis of multivesicular endosomes. J Cell Biol 139, 1183-95.

Harder, T., Kellner, R., Parton, R. G. and Gruenberg, J. (1997). Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol. Mol Biol Cell 8, 533-45.

Robinson, L. J., Aniento, F. and Gruenberg, J. (1997). NSF is required for transport from early to late endosomes. J Cell Sci 110 ( Pt 17), 2079-87.

Rojo, M., Budin, N., Kellner, R. and Gruenberg, J. (1997a). Generation of proteoliposomes from subcellular fractions. Electrophoresis 18, 2620-8.

Rojo, M., Pepperkok, R., Emery, G., Kellner, R., Stang, E., Parton, R. G. and Gruenberg, J. (1997b). Involvement of the transmembrane protein p23 in biosynthetic protein transport. J Cell Biol 139, 1119-35.

Kobayashi, T., Gu, F. and Gruenberg, J. (1998a). Lipids, lipid domains and lipid-protein interactions in endocytic membrane traffic. Semin Cell Dev Biol 9, 517-26.

Kobayashi, T., Stang, E., Fang, K. S., de Moerloose, P., Parton, R. G. and Gruenberg, J. (1998b). A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193-7.

Gu, F. and Gruenberg, J. (1999). Biogenesis of transport intermediates in the endocytic pathway. FEBS Lett 452, 61-6.

Kobayashi, T., Beuchat, M. H., Lindsay, M., Frias, S., Palmiter, R. D., Sakuraba, H., Parton, R. G. and Gruenberg, J. (1999). Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nat Cell Biol 1, 113-8.

Kobayashi, T. and Gruenberg, J. (1999). [Cell biology of lysobisphosphatidic acid]. Tanpakushitsu Kakusan Koso 44, 1181-6.

Piguet, V., Gu, F., Foti, M., Demaurex, N., Gruenberg, J., Carpentier, J. L. and Trono, D. (1999). Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 97, 63-73.

Bao, J., Alroy, I., Waterman, H., Schejter, E. D., Brodie, C., Gruenberg, J. and Yarden, Y. (2000). Threonine phosphorylation diverts internalized epidermal growth factor receptors from a degradative pathway to the recycling endosome. J Biol Chem 275, 26178-86.

Chevallier, J., Sakai, N., Robert, F., Kobayashi, T., Gruenberg, J. and Matile, S. (2000). Rapid access to synthetic lysobisphosphatidic acids using P(III) chemistry. Org Lett 2, 1859-61.

Emery, G., Rojo, M. and Gruenberg, J. (2000). Coupled transport of p24 family members. J Cell Sci 113 ( Pt 13), 2507-16.

Gagescu, R., Demaurex, N., Parton, R. G., Hunziker, W., Huber, L. A. and Gruenberg, J. (2000a). The recycling endosome of Madin-Darby canine kidney cells is a mildly acidic compartment rich in raft components. Mol Biol Cell 11, 2775-91.

Gagescu, R., Gruenberg, J. and Smythe, E. (2000b). Membrane dynamics in endocytosis: structure--function relationship. Traffic 1, 84-8.

Galve-de Rochemonteix, B., Kobayashi, T., Rosnoblet, C., Lindsay, M., Parton, R. G., Reber, G., de Maistre, E., Wahl, D., Kruithof, E. K., Gruenberg, J. et al. (2000). Interaction of anti-phospholipid antibodies with late endosomes of human endothelial cells. Arterioscler Thromb Vasc Biol 20, 563-74.

Gu, F. and Gruenberg, J. (2000). ARF1 regulates pH-dependent COP functions in the early endocytic pathway. J Biol Chem 275, 8154-60.

Huber, L. A., Fialka, I., Paiha, K., Hunziker, W., Sacks, D. B., Bahler, M., Way, M., Gagescu, R. and Gruenberg, J. (2000). Both calmodulin and the unconventional myosin Myr4 regulate membrane trafficking along the recycling pathway of MDCK cells. Traffic 1, 494-503.

Juuti-Uusitalo, K., Airenne, K. J., Laukkanen, A., Punnonen, E. L., Olkkonen, V. M., Gruenberg, J., Kulomaa, M. and Marjomaki, V. (2000). Selective targeting of avidin/mannose 6-phosphate receptor chimeras to early or late endosomes. Eur J Cell Biol 79, 458-68.

Kobayashi, T., Vischer, U. M., Rosnoblet, C., Lebrand, C., Lindsay, M., Parton, R. G., Kruithof, E. K. and Gruenberg, J. (2000). The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Mol Biol Cell 11, 1829-43.

Rojo, M., Emery, G., Marjomaki, V., McDowall, A. W., Parton, R. G. and Gruenberg, J. (2000). The transmembrane protein p23 contributes to the organization of the Golgi apparatus. J Cell Sci 113 ( Pt 6), 1043-57.

Simons, K. and Gruenberg, J. (2000). Jamming the endosomal system: lipid rafts and lysosomal storage diseases. Trends Cell Biol 10, 459-62.

Alpy, F., Stoeckel, M. E., Dierich, A., Escola, J. M., Wendling, C., Chenard, M. P., Vanier, M. T., Gruenberg, J., Tomasetto, C. and Rio, M. C. (2001). The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein. J Biol Chem 276, 4261-9.

Cavalli, V., Corti, M. and Gruenberg, J. (2001a). Endocytosis and signaling cascades: a close encounter. FEBS Lett 498, 190-6.

Cavalli, V., Vilbois, F., Corti, M., Marcote, M. J., Tamura, K., Karin, M., Arkinstall, S. and Gruenberg, J. (2001b). The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex. Mol Cell 7, 421-32.

Dunoyer-Geindre, S., Kruithof, E. K., Galve-de Rochemonteix, B., Rosnoblet, C., Gruenberg, J., Reber, G. and de Moerloose, P. (2001). Localization of beta2-glycoprotein 1 in late endosomes of human endothelial cells. Thromb Haemost 85, 903-7.

Fratti, R. A., Backer, J. M., Gruenberg, J., Corvera, S. and Deretic, V. (2001). Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J Cell Biol 154, 631-44.

Gruenberg, J. (2001). The endocytic pathway: a mosaic of domains. Nat Rev Mol Cell Biol 2, 721-30.

Felberbaum-Corti, M. and Gruenberg, J. (2002). Signaling from the far side. Mol Cell 10, 1259-60.

Kobayashi, T., Beuchat, M. H., Chevallier, J., Makino, A., Mayran, N., Escola, J. M., Lebrand, C., Cosson, P., Kobayashi, T. and Gruenberg, J. (2002). Separation and characterization of late endosomal membrane domains. J Biol Chem 277, 32157-64.

Lebrand, C., Corti, M., Goodson, H., Cosson, P., Cavalli, V., Mayran, N., Faure, J. and Gruenberg, J. (2002). Late endosome motility depends on lipids via the small GTPase Rab7. Embo J 21, 1289-300.

Incardona, J. P., Gruenberg, J. and Roelink, H. (2002). Sonic hedgehog induces the segregation of patched and smoothened in endosomes. Curr Biol 12, 983-95.

Sorice, M., Ferro, D., Misasi, R., Pittoni, V., Longo, A., Circella, A., Garofalo, T., Gradini, R., Violi, F., Gruenberg, J. et al. (2002). Evidence for anticoagulant activity and beta2-GPI accumulation in late endosomes of endothelial cells induced by anti-LBPA antibodies. Thromb Haemost 87, 735-41.

van der Goot, F. G. and Gruenberg, J. (2002). Oiling the wheels of the endocytic pathway. Trends Cell Biol 12, 296-9.

Vieira, O. V., Bucci, C., Harrison, R. E., Trimble, W. S., Lanzetti, L., Gruenberg, J., Schreiber, A. D., Stahl, P. D. and Grinstein, S. (2003). Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase. Mol Cell Biol 23, 2501-14.

Emery, G., Parton, R. G., Rojo, M. and Gruenberg, J. (2003). The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics. J Cell Sci 116, 4821-32.

Felberbaum-Corti, M., Van Der Goot, F. G. and Gruenberg, J. (2003). Sliding doors: clathrin-coated pits or caveolae? Nat Cell Biol 5, 382-4.

Fratti, R. A., Chua, J. and Deretic, V. (2003). Induction of p38 mitogen-activated protein kinase reduces early endosome autoantigen 1 (EEA1) recruitment to phagosomal membranes. J Biol Chem 278, 46961-7.

Gruenberg, J. (2003). Lipids in endocytic membrane transport and sorting. Curr Opin Cell Biol 15, 382-8.

Mayran, N., Parton, R. G. and Gruenberg, J. (2003). Annexin II regulates multivesicular endosome biogenesis in the degradation pathway of animal cells. Embo J 22, 3242-53.

Petiot, A., Faure, J., Stenmark, H. and Gruenberg, J. (2003). PI3P signaling regulates receptor sorting but not transport in the endosomal pathway. J Cell Biol 162, 971-9.

Faure, J., Stalder, R., Borel, C., Sobo, K., Piguet, V., Demaurex, N., Gruenberg, J. and Trono, D. (2004). ARF1 regulates Nef-induced CD4 degradation. Curr Biol 14, 1056-64.

Gruenberg, J. and Stenmark, H. (2004). The biogenesis of multivesicular endosomes. Nat Rev Mol Cell Biol 5, 317-23.

Matsuo, H., Chevallier, J., Mayran, N., Le Blanc, I., Ferguson, C., Faure, J., Blanc, N. S., Matile, S., Dubochet, J., Sadoul, R. et al. (2004). Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 303, 531-4.

Vieira, O. V., Harrison, R. E., Scott, C. C., Stenmark, H., Alexander, D., Liu, J., Gruenberg, J., Schreiber, A. D. and Grinstein, S. (2004). Acquisition of Hrs, an essential component of phagosomal maturation, is impaired by mycobacteria. Mol Cell Biol 24, 4593-604.

Alcon-LePoder, S., Drouet, M. T., Roux, P., Frenkiel, M. P., Arborio, M., Durand-Schneider, A. M., Maurice, M., Le Blanc, I., Gruenberg, J. and Flamand, M. (2005). The secreted form of dengue virus nonstructural protein NS1 is endocytosed by hepatocytes and accumulates in late endosomes: implications for viral infectivity. J Virol 79, 11403-11.

Felberbaum-Corti, M., Cavalli, V. and Gruenberg, J. (2005). Capture of the small GTPase Rab5 by GDI: regulation by p38 MAP kinase. Methods Enzymol 403, 367-81.

Jiang, G., Xu, Y., Falguieres, T., Gruenberg, J. and Prestwich, G. D. (2005). Concise synthesis of ether analogues of lysobisphosphatidic acid. Org Lett 7, 3837-40.

Le Blanc, I., Luyet, P. P., Pons, V., Ferguson, C., Emans, N., Petiot, A., Mayran, N., Demaurex, N., Faure, J., Sadoul, R. et al. (2005). Endosome-to-cytosol transport of viral nucleocapsids. Nat Cell Biol 7, 653-64.

Luyet, P. P. and Gruenberg, J. (2005). [Endocytosis: the Trojan Horse of viral infection]. Med Sci (Paris) 21, 909-10.

Gruenberg, J. and van der Goot, F. G. (2006a). Mechanisms of pathogen entry through the endosomal compartments. Nat Rev Mol Cell Biol 7, 495-504.

Gruenberg, J. and van der Goot, F. G. (2006b). Toxoplasma: guess who's coming to dinner. Cell 125, 226-8.

van der Goot, F. G. and Gruenberg, J. (2006). Intra-endosomal membrane transport. Trends Cell Biol 10, 514-21.

The Group