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Professor
Jean Gruenberg
Gruenberg in 2007
Born (1950-05-13) 13 May 1950 (age 74)
Academic work
DisciplineCell Biology
Sub-disciplineIntracellular 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.

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

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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

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Cell-free reconstitution of endosomal fission and fusion events

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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

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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

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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

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References

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  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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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.
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