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Galpha13 mediates a signal that is essential for proliferation and survival of thymocyte progenitors.

Authors
Type
Published Article
Journal
The Journal of experimental medicine
Publication Date
Volume
200
Issue
10
Pages
1315–1324
Identifiers
PMID: 15534370
Source
Medline
License
Unknown

Abstract

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.

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