Jean Gruenberg Explained

Honorific Prefix:Professor
Jean Gruenberg
Birth Date:13 May 1950
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.

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. Jean Gruenberg is married to Françoise Gisou van der Goot, and they have two children Sébastien and a girl.1950. 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] [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, 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] [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 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

External links

Notes and 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. 0014-2956. 710404. 10.1111/j.1432-1033.1978.tb12549.x. free.
  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. 0027-8424. 393533. 6341989. 10.1073/pnas.80.4.1087. 1983PNAS...80.1087G. free.
  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. 0261-4189. 1167298. 3028771. 10.1002/j.1460-2075.1986.tb04615.x.
  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. 0361-7742. 3045833.
  5. Howell. K. E.. Devaney. E.. Gruenberg. J.. 1989. Subcellular fractionation of tissue culture cells. Trends in Biochemical Sciences. 14. 2. 44–47. 0968-0004. 2705208. 10.1016/0968-0004(89)90040-6.
  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. 0021-9525. 2115527. 2538480. 10.1083/jcb.108.4.1301.
  7. 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. 0021-9525. 2290907. 8253838. 10.1083/jcb.123.6.1373.
  8. 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. 10.1016/S0021-9258(17)42302-7. 0021-9258. 8276796. free.
  9. Gu. F.. Gruenberg. J.. 1999-06-04. Biogenesis of transport intermediates in the endocytic pathway. FEBS Letters. 452. 1–2. 61–66. 0014-5793. 10376679. 10.1016/s0014-5793(99)00561-x. free.
  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. 0092-8674. 2143699. 10.1016/0092-8674(90)90117-w. 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. 10.1091/mbc.E15-12-0853. 1059-1524. 5170863. 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. 0092-8674. 1900457. 10.1016/0092-8674(91)90316-q. 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. 0261-4189. 394944. 8137813. 10.1002/j.1460-2075.1994.tb06381.x.
  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. 10.1093/emboj/21.6.1289. 0261-4189. 125356. 11889035.
  15. 1993-03-02. Annexin II is a major component of fusogenic endosomal vesicles. The Journal of Cell Biology. 120. 6. 1357–1369. 0021-9525. 2119741. 8449982. Emans. N.. Gorvel. J. P.. Walter. C.. Gerke. V.. Kellner. R.. Griffiths. G.. Gruenberg. J.. 10.1083/jcb.120.6.1357.
  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. 1059-1524. 276102. 9188103. 10.1091/mbc.8.3.533.
  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. 10.1093/emboj/cdg321. 0261-4189. 165635. 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. 10.1371/journal.pone.0001118. 1932-6203. 2040519. 17971878. 2007PLoSO...2.1118M. free.
  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. 10.1074/jbc.M806499200. 0021-9258. 18990701. free.
  20. Morel. Etienne. Parton. Robert G.. Gruenberg. Jean. 2009. Annexin A2-dependent polymerization of actin mediates endosome biogenesis. Developmental Cell. 16. 3. 445–457. 10.1016/j.devcel.2009.01.007. 1878-1551. 19289089. free.
  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. 0021-9525. 2120778. 8601610. 10.1083/jcb.133.1.29.
  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. 0021-9525. 2140201. 9382865. 10.1083/jcb.139.5.1183.
  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. 10.1242/jcs.110.17.2079. 0021-9533. 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. 0021-9525. 2140216. 9382861. 10.1083/jcb.139.5.1119.
  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. Journal of Cell Science. 113 (Pt 6). 6. 1043–1057. 10.1242/jcs.113.6.1043. 0021-9533. 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. 10.1242/jcs.113.13.2507. 0021-9533. 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. 10.1242/jcs.00802. 0021-9533. 14600267. free.
  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. 1097-2765. 11239470. 10.1016/s1097-2765(01)00189-7. free.
  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. 10.1083/jcb.200303018. 0021-9525. 2172844. 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. 10.1371/journal.pone.0000851. 1932-6203. 1952175. 17786222. 2007PLoSO...2..851S. free.
  31. 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. 10.1074/jbc.M801463200. 0021-9258. 18644787. free.
  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. 10.1371/journal.pone.0001144. 1932-6203. 2043495. 17987124. 2007PLoSO...2.1144F. free.
  33. 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. 10.1371/journal.pbio.0060214. 1544-9173. 2528051. 18767904 . free .
  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. 10.1371/journal.pone.0021771. 1932-6203. 3130770. 21754999. 2011PLoSO...621771B. free.
  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. 10.1371/journal.pone.0038949. 1932-6203. 3376135. 22719997. 2012PLoSO...738949P. free.
  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. 10.1091/mbc.E11-03-0193. 1059-1524. 3113771. 21525240.
  37. 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. 10.1126/science.1092425. 1095-9203. 14739459. 2004Sci...303..531M. 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. 10.1091/mbc.E08-03-0239. 1059-1524. 2575168. 18768755.
  39. 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. 10.1111/j.1600-0854.2008.00820.x. 1600-0854. 18817529. free.
  40. Falguières. Thomas. Castle. David. Gruenberg. Jean. 2012. Regulation of the MVB pathway by SCAMP3. Traffic. 13. 1. 131–142. 10.1111/j.1600-0854.2011.01291.x. 1600-0854. 21951651. free.
  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. 10.1038/ncb1269. 1465-7392. 3360589. 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. 10.1016/j.devcel.2013.04.003. 1534-5807. 4129370. 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. 10.1016/j.celrep.2013.10.019. 2211-1247. 3866279. 24239351.
  44. Bissig. Christin. Gruenberg. Jean. 2014. ALIX and the multivesicular endosome: ALIX in Wonderland. Trends in Cell Biology. 24. 1. 19–25. 10.1016/j.tcb.2013.10.009. 1879-3088. 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. 1523-7060. 10891176. 10.1021/ol0059246.
  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. 10.1038/32440. 0028-0836. 9515966. 1998Natur.392..193K. 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. 10.1038/10084. 1465-7392. 10559883. 15948485.

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