The Journal of Experimental Medicine
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Published online 8 November 2004 doi:10.1084/jem.20040944
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 10, 1315-1324
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G{alpha}13 Mediates a Signal That Is Essential for Proliferation and Survival of Thymocyte Progenitors

V. McNeil Coffield1,3, Whitney S. Helms2,3, Qi Jiang2,3, and Lishan Su1,2,3

1 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
2 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

Address correspondence to Lishan Su, Lineberger Comprehensive Cancer Center, Dept. of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7295. Phone: (919) 966-6654; Fax: (919) 966-8212; email: lsu{at}med.unc.edu

G protein signaling via the G{alpha}12 family (G{alpha}12 and G{alpha}13) has not been well studied in T cells. To investigate whether G{alpha}12 and G{alpha}13 are involved in thymopoiesis, we expressed the regulator of G protein signaling domain of p115RhoGEF to inhibit G{alpha}12 and G{alpha}13 during thymopoiesis. Fetal thymus organ cultures seeded with p115{Delta}DH-expressing progenitor cells showed impaired thymopoiesis with a block at the CD4–CD8–CD44–CD25+ (DN3) stage. Using G{alpha}13 or G{alpha}12 minigenes, we demonstrated that G{alpha}13, but not G{alpha}12, is required for thymopoiesis. T progenitor cells expressing p115{Delta}DH showed reduced proliferation and increased cell death. T cell receptor stimulation of the fetal thymus organ cultures did not rescue the block. Overexpression of the antiapoptotic gene Bcl2 rescued the defect in DN3 cells and partially rescued T cell development. Therefore, G{alpha}13-mediated signaling is necessary in early thymocyte proliferation and survival.

Key Words: thymopoiesis • G protein • p115RhoGEF • RhoA • RGS

V. McNeil Coffield and W.S. Helms contributed equally to this work.

Abbreviations used in this paper: 2-dG, 2-deoxyguanosine; DH, Dbl homology; DN, double negative; DP, double positive; E, embryonic day; FL, fetal liver; FTOC, fetal thymus organ culture; GFP, green fluorescent protein; GPCR, G protein–coupled receptor; LPC, lysophosphatidylcholine; PH, plextrin homology; RGS, regulator of G protein signaling.


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