Galpha13 mediates a signal that is essential for proliferation and survival of thymocyte progenitors.
G protein signaling via the Galpha12 family (Galpha12 and Galpha13) has not been well studied in T cells. To investigate whether Galpha12 and Galpha13 are involved in thymopoiesis, we expressed the regulator of G protein signaling domain of p115RhoGEF to inhibit Galpha12 and Galpha13 during thymopoiesis. Fetal thymus organ cultures seeded with p115DeltaDH-expressing progenitor cells showed impaired thymopoiesis with a block at the CD4-CD8-CD44-CD25+ (DN3) stage. Using Galpha13 or Galpha12 minigenes, we demonstrated that Galpha13, but not Galpha12, is required for thymopoiesis. T progenitor cells expressing p115DeltaDH 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, Galpha13-mediated signaling is necessary in early thymocyte proliferation and survival.
Coffield
V McNeil
VM
Lineberger Comprehensive Cancer Center, Dept. of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
Helms
Whitney S
WS
Jiang
Qi
Q
Su
Lishan
L
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005434:Flow Cytometry; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism / Q000502:physiology*; D005822:Genetic Vectors; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D051379:Mice; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology
D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D044365:GTP-Binding Protein alpha Subunits, G12-G13