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Rac GTPases play critical roles in early T-cell development

Dumont, Celine, Corsoni-Tadrzak, Agnieszka, Ruf, Sandra, de Boer, Jasper, Williams, Adam, Turner, Martin, Kioussis, Dimitris, Tybulewicz, Victor L. J.·2009·Blood
DOI 10.1182/blood-2008-09-181180
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Abstract

The Rac1 and Rac2 GTPases play important roles in many processes including cytoskeletal reorganization, proliferation, and survival, and are required for B-cell development. Previous studies had shown that deficiency in Rac2 did not affect T-cell development, whereas the function of Rac1 in this process has not been investigated. We now show that simultaneous absence of both GTPases resulted in a very strong developmental block at the pre-TCR checkpoint and in defective positive selection. Unexpectedly, deficiency of Rac1 and Rac2 also resulted in the aberrant survival of thymocytes lacking expression of TCRβ, showing hallmarks of hyperactive Notch signaling. Furthermore, we found a similar novel phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine nucleotide exchange factors for Rac1 and Rac2. These results show that a pathway containing Vav and Rac proteins may negatively regulate Notch signaling during early thymic development.

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  1. Ciofani, 2007, The thymus as an inductive site for T lymphopoiesis., Annu Rev Cell Dev Biol, 23, 463, 10.1146/annurev.cellbio.23.090506.123547 · DOI
  2. Tybulewicz, 2005, Vav-family proteins in T-cell signalling., Curr Opin Immunol, 17, 267, 10.1016/j.coi.2005.04.003 · DOI
  3. Fujikawa, 2003, Vav1/2/3-null mice define an essential role for Vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells., J Exp Med, 198, 1595, 10.1084/jem.20030874 · DOI
  4. Turner, 1997, A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes., Immunity, 7, 451, 10.1016/S1074-7613(00)80367-2 · DOI
  5. Ridley, 2006, Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking., Trends Cell Biol, 16, 522, 10.1016/j.tcb.2006.08.006 · DOI
  6. Walmsley, 2003, Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling., Science, 302, 459, 10.1126/science.1089709 · DOI · Paper page
  7. Gomez, 2000, Control of pre-T cell proliferation and differentiation by the GTPase Rac-1., Nat Immunol, 1, 348, 10.1038/79808 · DOI
  8. Gomez, 2001, The GTPase Rac-1 controls cell fate in the thymus by diverting thymocytes from positive to negative selection., Immunity, 15, 703, 10.1016/S1074-7613(01)00235-7 · DOI
  9. Lorès, 1997, Enhanced apoptosis in the thymus of transgenic mice expressing constitutively activated forms of human Rac2GTPase., Oncogene, 15, 601, 10.1038/sj.onc.1201378 · DOI · Paper page
  10. Croker, 2002, Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in T(H)1 responses., Immunol Cell Biol, 80, 231, 10.1046/j.1440-1711.2002.01077.x · DOI
  11. Yu, 2001, Deficiency of small GTPase Rac2 affects T cell activation., J Exp Med, 194, 915, 10.1084/jem.194.7.915 · DOI
  12. Sugihara, 1998, Rac1 is required for the formation of three germ layers during gastrulation., Oncogene, 17, 3427, 10.1038/sj.onc.1202595 · DOI
  13. Nombela-Arrieta, 2004, Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing., Immunity, 21, 429, 10.1016/j.immuni.2004.07.012 · DOI
  14. Sanui, 2003, DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells., Immunity, 19, 119, 10.1016/S1074-7613(03)00169-9 · DOI
  15. Fanzo, 2006, Loss of IRF-4-binding protein leads to the spontaneous development of systemic autoimmunity., J Clin Invest, 116, 703, 10.1172/JCI24096 · DOI
  16. Bécart, 2007, SLAT regulates Th1 and Th2 inflammatory responses by controlling Ca2+/NFAT signaling., J Clin Invest, 117, 2164, 10.1172/JCI31640 · DOI
  17. Roberts, 1999, Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense., Immunity, 10, 183, 10.1016/S1074-7613(00)80019-9 · DOI · Paper page
  18. de Boer, 2003, Transgenic mice with hematopoietic and lymphoid specific expression of Cre., Eur J Immunol, 33, 314, 10.1002/immu.200310005 · DOI · Paper page
  19. Mamalaki, 1993, Positive and negative selection in transgenic mice expressing a T-cell receptor specific for influenza nucleoprotein and endogenous superantigen., Dev Immunol, 3, 159, 10.1155/1993/98015 · DOI
  20. Spanopoulou, 1994, Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice., Genes Dev, 8, 1030, 10.1101/gad.8.9.1030 · DOI
  21. Vigorito, 2005, Vav proteins regulate peripheral B-cell survival., Blood, 106, 2391, 10.1182/blood-2004-12-4894 · DOI
  22. Starr, 2003, Positive and negative selection of T cells., Annu Rev Immunol, 21, 139, 10.1146/annurev.immunol.21.120601.141107 · DOI · Paper page
  23. Ladi, 2006, Thymic microenvironments for T cell differentiation and selection., Nat Immunol, 7, 338, 10.1038/ni1323 · DOI
  24. Falk, 2001, Immature thymocytes that fail to express TCRbeta and/or TCRgamma delta proteins die by apoptotic cell death in the CD44(-)CD25(-) (DN4) subset., Eur J Immunol, 31, 3308, 10.1002/1521-4141(200111)31:11<3308::AID-IMMU3308>3.0.CO;2-5 · DOI
  25. Yu, 2004, IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat: impact on thymocyte development., J Exp Med, 200, 797, 10.1084/jem.20032183 · DOI
  26. von Freeden-Jeffry, 1997, The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression., Immunity, 7, 147, 10.1016/S1074-7613(00)80517-8 · DOI
  27. Luo, 1997, Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptor., Mol Cell Biol, 17, 6057, 10.1128/MCB.17.10.6057 · DOI
  28. García-Peydró, 2006, Notch1 and IL-7 receptor interplay maintains proliferation of human thymic progenitors while suppressing non-T cell fates., J Immunol, 177, 3711, 10.4049/jimmunol.177.6.3711 · DOI
  29. Fischer, 1998, Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor., Curr Biol, 8, 554, 10.1016/S0960-9822(98)70224-6 · DOI
  30. Holsinger, 1998, Defects in actin cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction., Curr Biol, 8, 563, 10.1016/S0960-9822(98)70225-8 · DOI
  31. Costello, 1999, The Rho-family GTP exchange factor Vav is a critical transducer of TCR signals to the calcium, ERK and NF-kB pathways., Proc Natl Acad Sci U S A, 96, 3035, 10.1073/pnas.96.6.3035 · DOI
  32. Reynolds, 2002, Vav1 transduces T cell receptor signals to the activation of phospholipase C-γ1 via phosphoinositide 3-kinase-dependent and -independent pathways., J Exp Med, 195, 1103, 10.1084/jem.20011663 · DOI
  33. Reynolds, 2004, Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos and RasGRP1., J Biol Chem, 279, 18239, 10.1074/jbc.M400257200 · DOI
  34. Ardouin, 2003, Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse., Eur J Immunol, 33, 790, 10.1002/eji.200323858 · DOI
  35. Krawczyk, 2002, Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells., Immunity, 16, 331, 10.1016/S1074-7613(02)00291-1 · DOI
  36. Kuhne, 2000, A guanine nucleotide exchange factor-independent function of Vav1 in transcriptional activation., J Biol Chem, 275, 2185, 10.1074/jbc.275.3.2185 · DOI
  37. Tybulewicz, 2003, Vav1: a key signal transducer downstream of the TCR., Immunol Rev, 192, 42, 10.1034/j.1600-065X.2003.00032.x · DOI
  38. Guo, 2008, Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development., Blood, 112, 1767, 10.1182/blood-2008-01-132068 · DOI · Paper page
  39. Bellavia, 2000, Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice., EMBO J, 19, 3337, 10.1093/emboj/19.13.3337 · DOI
  40. Tanigaki, 2004, Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling., Immunity, 20, 611, 10.1016/S1074-7613(04)00109-8 · DOI
  41. Wolfer, 2002, Inactivation of Notch1 impairs VDJβ rearrangement and allows pre-TCR-independent survival of early αβ lineage., Immunity, 16, 869, 10.1016/S1074-7613(02)00330-8 · DOI
  42. Huang, 2003, Surface expression of Notch1 on thymocytes: correlation with the double-negative to double-positive transition., J Immunol, 171, 2296, 10.4049/jimmunol.171.5.2296 · DOI
  43. Fischer, 2005, The Role of Erk1 and Erk2 in multiple stages of T cell development., Immunity, 23, 431, 10.1016/j.immuni.2005.08.013 · DOI
  44. Baron, 2000, Multiple roles of the Dcdc42 GTPase during wing development in Drosophila melanogaster., Mol Gen Genet, 264, 98, 10.1007/s004380000287 · DOI
  45. Yoo, 2005, LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans., Science, 310, 1330, 10.1126/science.1119481 · DOI

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Metadata

Authors
Dumont, C., Corsoni-Tadrzak, A., Ruf, S., de Boer, J., Williams, A., Turner, M., Kioussis, D., & Tybulewicz, V. L. J.
Affiliations
  • Divisions of Immune Cell Biology and
  • Molecular Immunology, Medical Research Council (MRC) National Institute for Medical Research, London; and
  • The Babraham Institute, Cambridge, United Kingdom
Venue
Blood
Publisher
American Society of Hematology
Published
2009-04-23
Volume
113
Issue
17
Pages
3990-3998
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2008-09-181180
Cited by
66
References
3
Language
en

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CoChat. (2026). Citation check: Rac GTPases play critical roles in early T-cell development. https://app.cochat.ai/papers/10.1182/blood-2008-09-181180
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Dumont, C., Corsoni-Tadrzak, A., Ruf, S., de Boer, J., Williams, A., Turner, M., Kioussis, D., & Tybulewicz, V. L. J. (2009). Rac GTPases play critical roles in early T-cell development. Blood. https://doi.org/10.1182/blood-2008-09-181180