Jean Gruenberg

Last updated
Professor
Jean Gruenberg
Jean Gruenberg.jpg
Gruenberg in 2007
Born (1950-05-13) 13 May 1950 (age 75)
Academic work
Discipline Cell Biology
Sub-discipline Intracellular Trafficking

Jean Gruenberg (born May 13, 1950) is a Swiss biologist, and a professor at the University of Geneva. His research in the fields of cell biology and biochemistry has significantly contributed to a better understanding of the molecular mechanisms involved in the intracellular traffic within eukaryotic cells, more especially in the endolysosomal pathway.

Contents

Using innovative approaches such as phospholipid-specific antibodies and reconstituted cell-free systems, Jean Gruenberg and his colleagues were able to unravel several important mechanisms regulating the biogenesis and membrane dynamics of early and late endosomal compartments.

Biography

Jean Gruenberg was born in Switzerland in 1950.[ citation needed ] Jean Gruenberg is married to Françoise Gisou van der Goot, and they have two children Sébastien and a girl.1950.[ citation needed ] Jean Gruenberg and his family reside in Trelex Switzerland and he works at the University of Geneva as an emeritus professor in the Department of Biochemistry.

Scientific achievements

Cell-free reconstitution of endosomal fission and fusion events

After early studies on parasites (T. brucei and P. falciparum), [1] [2] Jean Gruenberg switched focus and studied the dynamics endosomal processes when he started to work at the European Molecular Biology Laboratory (EMBL) with Kate Howell, and made several important discoveries on the molecular factors directing endosome dynamics, and was successful in reconstituting the process in vitro. [3] [4] [5] [6] When he became an independent investigator, first at the EMBL and then at the University of Geneva, he continued this line of research and worked on the characterization of early and late endosomes, and identified a transport intermediate between these organelles known as the ECVs/MVBs (Early Carrier Vesicles / MultiVesicular Bodies). [7] [8] [9]

Molecular mechanisms of endosomal biogenesis and membrane dynamics

Throughout his career, Jean Gruenberg and his colleagues identified several molecular factors directing endosomal biogenesis and dynamics, including various cytoskeleton-associated proteins, [10] [7] [11] the small GTPases Rab5 [12] [13] and Rab7, [14] Annexin A2 (previously named Annexin II), [15] [16] [17] [18] [19] [20] the vacuolar ATPase, [8] COP coat proteins, [21] [22] the N-ethylmaleimide sensitive factor, [23] the small transmembrane proteins of the p24 family, [24] [25] [26] [27] the p38 MAP kinase, [28] phosphatidylinositol-3-phosphate, [29] intra-endosomal cholesterol, [30] [31] the redox sensor thioredoxin-like protein, [32] sorting nexins, [33] [34] [35] the adaptor protein complex AP1, [36] components of ESCRTs and associated proteins [37] [33] [38] [39] [40] and the atypical phospholipid LBPA/BMP (see next section).

Using the Vesicular Stomatitis Virus (VSV) as a "hijacker" of the endocytic pathway, Jean Gruenberg and his colleagues demonstrated that intralumenal vesicles present within multivesicular endosomes are able to undergo back-fusion with the limiting membrane of these organelles, thus releasing their content into the cytoplasm, [41] a process regulated by the ESCRT-related proteins TSG101 [39] and ALIX, [42] and since shown to be exploited by various other invaders of the cells such as the Anthrax toxin, [43] and several other viruses. [44]

Characterization of lysobisphosphatidic acid using anti-phospholipid antibodies

A milestone discovery in the career of Jean Gruenberg was the identification and the characterization of an atypical inverted cone-shaped phospholipid, [45] originally named lysobisphosphatidic acid (LBPA) and also known as bis(monoacylglycero)phosphate (BMP). Using specific monoclonal antibodies, LBPA/BMP was shown to be enriched in intralumenal vesicles of late endosomes [46] and to regulate the intracellular transport and homeostasis of cholesterol. [47] [31] LBPA/BMP is also directly involved in the formation of intracellular vesicles within multivesicular endosomes and endosome-mimicking liposomes. [37]

See also

References

  1. Gruenberg, J.; Sharma, P. R.; Deshusses, J. (1978-09-01). "D-Glucose transport in Trypanosoma brucei. D-Glucose transport is the rate-limiting step of its metabolism". European Journal of Biochemistry. 89 (2): 461–469. doi: 10.1111/j.1432-1033.1978.tb12549.x . ISSN   0014-2956. PMID   710404.
  2. Gruenberg, J.; Sherman, I. W. (1983). "Isolation and characterization of the plasma membrane of human erythrocytes infected with the malarial parasite Plasmodium falciparum". Proceedings of the National Academy of Sciences of the United States of America. 80 (4): 1087–1091. Bibcode:1983PNAS...80.1087G. doi: 10.1073/pnas.80.4.1087 . ISSN   0027-8424. PMC   393533 . PMID   6341989.
  3. Gruenberg, J. E.; Howell, K. E. (1986-12-01). "Reconstitution of vesicle fusions occurring in endocytosis with a cell-free system". The EMBO Journal. 5 (12): 3091–3101. doi:10.1002/j.1460-2075.1986.tb04615.x. ISSN   0261-4189. PMC   1167298 . PMID   3028771.
  4. Gruenberg, J.; Howell, K. E. (1988). "Fusion in the endocytic pathway reconstituted in a cell-free system using immuno-isolated fractions". Progress in Clinical and Biological Research. 270: 317–331. ISSN   0361-7742. PMID   3045833.
  5. Howell, K. E.; Devaney, E.; Gruenberg, J. (1989). "Subcellular fractionation of tissue culture cells". Trends in Biochemical Sciences. 14 (2): 44–47. doi:10.1016/0968-0004(89)90040-6. ISSN   0968-0004. PMID   2705208.
  6. Gruenberg, J.; Griffiths, G.; Howell, K. E. (1989). "Characterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro". The Journal of Cell Biology. 108 (4): 1301–1316. doi:10.1083/jcb.108.4.1301. ISSN   0021-9525. PMC   2115527 . PMID   2538480.
  7. 1 2 Aniento, F.; Emans, N.; Griffiths, G.; Gruenberg, J. (1993). "Cytoplasmic dynein-dependent vesicular transport from early to late endosomes". The Journal of Cell Biology. 123 (6 Pt 1): 1373–1387. doi:10.1083/jcb.123.6.1373. ISSN   0021-9525. PMC   2290907 . PMID   8253838.
  8. 1 2 Clague, M. J.; Urbé, S.; Aniento, F.; Gruenberg, J. (1994-01-07). "Vacuolar ATPase activity is required for endosomal carrier vesicle formation". The Journal of Biological Chemistry. 269 (1): 21–24. doi: 10.1016/S0021-9258(17)42302-7 . ISSN   0021-9258. PMID   8276796.
  9. Gu, F.; Gruenberg, J. (1999-06-04). "Biogenesis of transport intermediates in the endocytic pathway". FEBS Letters. 452 (1–2): 61–66. doi: 10.1016/s0014-5793(99)00561-x . ISSN   0014-5793. PMID   10376679.
  10. Bomsel, M.; Parton, R.; Kuznetsov, S. A.; Schroer, T. A.; Gruenberg, J. (1990-08-24). "Microtubule- and motor-dependent fusion in vitro between apical and basolateral endocytic vesicles from MDCK cells". Cell. 62 (4): 719–731. doi:10.1016/0092-8674(90)90117-w. ISSN   0092-8674. PMID   2143699. S2CID   31624175.
  11. Muriel, Olivia; Tomas, Alejandra; Scott, Cameron C.; Gruenberg, Jean (2016-11-01). "Moesin and cortactin control actin-dependent multivesicular endosome biogenesis". Molecular Biology of the Cell. 27 (21): 3305–3316. doi:10.1091/mbc.E15-12-0853. ISSN   1059-1524. PMC   5170863 . PMID   27605702.
  12. Gorvel, J. P.; Chavrier, P.; Zerial, M.; Gruenberg, J. (1991-03-08). "rab5 controls early endosome fusion in vitro". Cell. 64 (5): 915–925. doi:10.1016/0092-8674(91)90316-q. ISSN   0092-8674. PMID   1900457. S2CID   38615225.
  13. Stenmark, H.; Parton, R. G.; Steele-Mortimer, O.; Lütcke, A.; Gruenberg, J.; Zerial, M. (1994-03-15). "Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis". The EMBO Journal. 13 (6): 1287–1296. doi:10.1002/j.1460-2075.1994.tb06381.x. ISSN   0261-4189. PMC   394944 . PMID   8137813.
  14. Lebrand, Cécile; Corti, Michela; Goodson, Holly; Cosson, Pierre; Cavalli, Valeria; Mayran, Nathalie; Fauré, Julien; Gruenberg, Jean (2002-03-15). "Late endosome motility depends on lipids via the small GTPase Rab7". The EMBO Journal. 21 (6): 1289–1300. doi:10.1093/emboj/21.6.1289. ISSN   0261-4189. PMC   125356 . PMID   11889035.
  15. Emans, N.; Gorvel, J. P.; Walter, C.; Gerke, V.; Kellner, R.; Griffiths, G.; Gruenberg, J. (1993-03-02). "Annexin II is a major component of fusogenic endosomal vesicles". The Journal of Cell Biology. 120 (6): 1357–1369. doi:10.1083/jcb.120.6.1357. ISSN   0021-9525. PMC   2119741 . PMID   8449982.
  16. Harder, T.; Kellner, R.; Parton, R. G.; Gruenberg, J. (1997). "Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol". Molecular Biology of the Cell. 8 (3): 533–545. doi:10.1091/mbc.8.3.533. ISSN   1059-1524. PMC   276102 . PMID   9188103.
  17. Mayran, Nathalie; Parton, Robert G.; Gruenberg, Jean (2003-07-01). "Annexin II regulates multivesicular endosome biogenesis in the degradation pathway of animal cells". The EMBO Journal. 22 (13): 3242–3253. doi:10.1093/emboj/cdg321. ISSN   0261-4189. PMC   165635 . PMID   12839987.
  18. Morel, Etienne; Gruenberg, Jean (2007-10-31). "The p11/S100A10 Light Chain of Annexin A2 Is Dispensable for Annexin A2 Association to Endosomes and Functions in Endosomal Transport". PLOS ONE. 2 (10) e1118. Bibcode:2007PLoSO...2.1118M. doi: 10.1371/journal.pone.0001118 . ISSN   1932-6203. PMC   2040519 . PMID   17971878.
  19. Morel, Etienne; Gruenberg, Jean (2009-01-16). "Annexin A2 binding to endosomes and functions in endosomal transport are regulated by tyrosine 23 phosphorylation". The Journal of Biological Chemistry. 284 (3): 1604–1611. doi: 10.1074/jbc.M806499200 . ISSN   0021-9258. PMID   18990701.
  20. Morel, Etienne; Parton, Robert G.; Gruenberg, Jean (2009). "Annexin A2-dependent polymerization of actin mediates endosome biogenesis". Developmental Cell. 16 (3): 445–457. doi: 10.1016/j.devcel.2009.01.007 . ISSN   1878-1551. PMID   19289089.
  21. Aniento, F.; Gu, F.; Parton, R. G.; Gruenberg, J. (1996). "An endosomal beta COP is involved in the pH-dependent formation of transport vesicles destined for late endosomes". The Journal of Cell Biology. 133 (1): 29–41. doi:10.1083/jcb.133.1.29. ISSN   0021-9525. PMC   2120778 . PMID   8601610.
  22. Gu, Feng; Aniento, Fernando; Parton, Robert G.; Gruenberg, Jean (1997-12-01). "Functional Dissection of COP-I Subunits in the Biogenesis of Multivesicular Endosomes". The Journal of Cell Biology. 139 (5): 1183–1195. doi:10.1083/jcb.139.5.1183. ISSN   0021-9525. PMC   2140201 . PMID   9382865.
  23. Robinson, L. J.; Aniento, F.; Gruenberg, J. (1997). "NSF is required for transport from early to late endosomes". Journal of Cell Science. 110 ( Pt 17) (17): 2079–2087. doi:10.1242/jcs.110.17.2079. ISSN   0021-9533. PMID   9378758.
  24. Rojo, M.; Pepperkok, R.; Emery, G.; Kellner, R.; Stang, E.; Parton, R. G.; Gruenberg, J. (1997-12-01). "Involvement of the transmembrane protein p23 in biosynthetic protein transport". The Journal of Cell Biology. 139 (5): 1119–1135. doi:10.1083/jcb.139.5.1119. ISSN   0021-9525. PMC   2140216 . PMID   9382861.
  25. Rojo, M.; Emery, G.; Marjomäki, V.; McDowall, A. W.; Parton, R. G.; Gruenberg, J. (2000). "The transmembrane protein p23 contributes to the organization of the Golgi apparatus" (PDF). Journal of Cell Science. 113 ( Pt 6) (6): 1043–1057. doi:10.1242/jcs.113.6.1043. ISSN   0021-9533. PMID   10683152.
  26. Emery, G.; Rojo, M.; Gruenberg, J. (2000). "Coupled transport of p24 family members". Journal of Cell Science. 113 ( Pt 13) (13): 2507–2516. doi:10.1242/jcs.113.13.2507. ISSN   0021-9533. PMID   10852829.
  27. Emery, Gregory; Parton, Robert G.; Rojo, Manuel; Gruenberg, Jean (2003-12-01). "The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics". Journal of Cell Science. 116 (Pt 23): 4821–4832. doi: 10.1242/jcs.00802 . ISSN   0021-9533. PMID   14600267.
  28. Cavalli, V.; Vilbois, F.; Corti, M.; Marcote, M. J.; Tamura, K.; Karin, M.; Arkinstall, S.; Gruenberg, J. (2001). "The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex". Molecular Cell. 7 (2): 421–432. doi: 10.1016/s1097-2765(01)00189-7 . ISSN   1097-2765. PMID   11239470.
  29. Petiot, A.; Faure, J.; Stenmark, H.; Gruenberg, J. (2003-09-15). "PI3P signaling regulates receptor sorting but not transport in the endosomal pathway". The Journal of Cell Biology. 162 (6): 971–979. doi:10.1083/jcb.200303018. ISSN   0021-9525. PMC   2172844 . PMID   12975344.
  30. Sobo, Komla; Le Blanc, Isabelle; Luyet, Pierre-Philippe; Fivaz, Marc; Ferguson, Charles; Parton, Robert G.; Gruenberg, Jean; van der Goot, F. Gisou (2007-09-05). "Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking". PLOS ONE. 2 (9) e851. Bibcode:2007PLoSO...2..851S. doi: 10.1371/journal.pone.0000851 . ISSN   1932-6203. PMC   1952175 . PMID   17786222.
  31. 1 2 Chevallier, Julien; Chamoun, Zeina; Jiang, Guowei; Prestwich, Glenn; Sakai, Naomi; Matile, Stefan; Parton, Robert G.; Gruenberg, Jean (2008-10-10). "Lysobisphosphatidic acid controls endosomal cholesterol levels". The Journal of Biological Chemistry. 283 (41): 27871–27880. doi: 10.1074/jbc.M801463200 . ISSN   0021-9258. PMID   18644787.
  32. Felberbaum-Corti, Michela; Morel, Etienne; Cavalli, Valeria; Vilbois, Francis; Gruenberg, Jean (2007-11-07). "The Redox Sensor TXNL1 Plays a Regulatory Role in Fluid Phase Endocytosis". PLOS ONE. 2 (11) e1144. Bibcode:2007PLoSO...2.1144F. doi: 10.1371/journal.pone.0001144 . ISSN   1932-6203. PMC   2043495 . PMID   17987124.
  33. 1 2 Pons, Véronique; Luyet, Pierre-Philippe; Morel, Etienne; Abrami, Laurence; van der Goot, F. Gisou; Parton, Robert G; Gruenberg, Jean (2008). "Hrs and SNX3 Functions in Sorting and Membrane Invagination within Multivesicular Bodies". PLOS Biology. 6 (9) e214. doi: 10.1371/journal.pbio.0060214 . ISSN   1544-9173. PMC   2528051 . PMID   18767904.
  34. Brankatschk, Ben; Pons, Véronique; Parton, Robert G.; Gruenberg, Jean (2011-07-06). "Role of SNX16 in the Dynamics of Tubulo-Cisternal Membrane Domains of Late Endosomes". PLOS ONE. 6 (7) e21771. Bibcode:2011PLoSO...621771B. doi: 10.1371/journal.pone.0021771 . ISSN   1932-6203. PMC   3130770 . PMID   21754999.
  35. Pons, Véronique; Ustunel, Cansel; Rolland, Corinne; Torti, Eleonora; Parton, Robert G.; Gruenberg, Jean (2012-06-15). "SNX12 Role in Endosome Membrane Transport". PLOS ONE. 7 (6) e38949. Bibcode:2012PLoSO...738949P. doi: 10.1371/journal.pone.0038949 . ISSN   1932-6203. PMC   3376135 . PMID   22719997.
  36. Laulagnier, Karine; Schieber, Nicole L.; Maritzen, Tanja; Haucke, Volker; Parton, Robert G.; Gruenberg, Jean (2011-06-15). "Role of AP1 and Gadkin in the traffic of secretory endo-lysosomes". Molecular Biology of the Cell. 22 (12): 2068–2082. doi:10.1091/mbc.E11-03-0193. ISSN   1059-1524. PMC   3113771 . PMID   21525240.
  37. 1 2 Matsuo, Hirotami; Chevallier, Julien; Mayran, Nathalie; Le Blanc, Isabelle; Ferguson, Charles; Fauré, Julien; Blanc, Nathalie Sartori; Matile, Stefan; Dubochet, Jacques (2004-01-23). "Role of LBPA and Alix in multivesicular liposome formation and endosome organization". Science. 303 (5657): 531–534. Bibcode:2004Sci...303..531M. doi:10.1126/science.1092425. ISSN   1095-9203. PMID   14739459. S2CID   36353407.
  38. Falguières, Thomas; Luyet, Pierre-Philippe; Bissig, Christin; Scott, Cameron C.; Velluz, Marie-Claire; Gruenberg, Jean (2008). "In Vitro Budding of Intralumenal Vesicles into Late Endosomes Is Regulated by Alix and Tsg101". Molecular Biology of the Cell. 19 (11): 4942–4955. doi:10.1091/mbc.E08-03-0239. ISSN   1059-1524. PMC   2575168 . PMID   18768755.
  39. 1 2 Luyet, Pierre-Philippe; Falguières, Thomas; Pons, Véronique; Pattnaik, Asit K.; Gruenberg, Jean (2008). "The ESCRT-I subunit TSG101 controls endosome-to-cytosol release of viral RNA". Traffic. 9 (12): 2279–2290. doi: 10.1111/j.1600-0854.2008.00820.x . ISSN   1600-0854. PMID   18817529.
  40. Falguières, Thomas; Castle, David; Gruenberg, Jean (2012). "Regulation of the MVB pathway by SCAMP3". Traffic. 13 (1): 131–142. doi: 10.1111/j.1600-0854.2011.01291.x . ISSN   1600-0854. PMID   21951651.
  41. Le Blanc, Isabelle; Luyet, Pierre-Philippe; Pons, Véronique; Ferguson, Charles; Emans, Neil; Petiot, Anne; Mayran, Nathalie; Demaurex, Nicolas; Fauré, Julien (2005). "Endosome-to-cytosol transport of viral nucleocapsids". Nature Cell Biology. 7 (7): 653–664. doi:10.1038/ncb1269. ISSN   1465-7392. PMC   3360589 . PMID   15951806.
  42. Bissig, Christin; Lenoir, Marc; Velluz, Marie-Claire; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael; Gruenberg, Jean (2013-05-28). "Viral infection controlled by a calcium-dependent lipid-binding module in ALIX". Developmental Cell. 25 (4): 364–373. doi:10.1016/j.devcel.2013.04.003. ISSN   1534-5807. PMC   4129370 . PMID   23664863.
  43. Abrami, Laurence; Brandi, Lucia; Moayeri, Mahtab; Brown, Michael J.; Krantz, Bryan A.; Leppla, Stephen H.; van der Goot, F. Gisou (2013-11-27). "Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin". Cell Reports. 5 (4): 986–996. doi:10.1016/j.celrep.2013.10.019. ISSN   2211-1247. PMC   3866279 . PMID   24239351.
  44. Bissig, Christin; Gruenberg, Jean (2014). "ALIX and the multivesicular endosome: ALIX in Wonderland". Trends in Cell Biology. 24 (1): 19–25. doi:10.1016/j.tcb.2013.10.009. ISSN   1879-3088. PMID   24287454.
  45. Chevallier, J.; Sakai, N.; Robert, F.; Kobayashi, T.; Gruenberg, J.; Matile, S. (2000-06-29). "Rapid access to synthetic lysobisphosphatidic acids using P(III) chemistry". Organic Letters. 2 (13): 1859–1861. doi:10.1021/ol0059246. ISSN   1523-7060. PMID   10891176.
  46. Kobayashi, T.; Stang, E.; Fang, K. S.; de Moerloose, P.; Parton, R. G.; Gruenberg, J. (1998-03-12). "A lipid associated with the antiphospholipid syndrome regulates endosome structure and function". Nature. 392 (6672): 193–197. Bibcode:1998Natur.392..193K. doi:10.1038/32440. ISSN   0028-0836. PMID   9515966. S2CID   4322776.
  47. Kobayashi, T.; Beuchat, M. H.; Lindsay, M.; Frias, S.; Palmiter, R. D.; Sakuraba, H.; Parton, R. G.; Gruenberg, J. (1999). "Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport". Nature Cell Biology. 1 (2): 113–118. doi:10.1038/10084. ISSN   1465-7392. PMID   10559883. S2CID   15948485.