αPIX RhoGEF supports positive selection by restraining migration and promoting arrest of thymocytes.
J Immunol
; 192(7): 3228-38, 2014 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-24591366
ABSTRACT
Thymocytes mature in a series of stages by migrating through specific areas of the thymus and interacting with other cells to receive the necessary developmental signals; however, little is known about the molecular mechanisms governing this migration. We report that murine thymocytes with a knockout mutation in α-PAK (p21-activated kinase)-interacting exchange factor (PIX; Arhgef6), an activator of Rho GTPases, showed greatly increased motility and altered morphology in two-dimensional migration on ICAM-1. αPIX was also required for efficient positive selection, but not negative selection, of thymocytes. TCR signaling was normal in αPix(-) thymocytes, indicating that the effects of αPIX on positive selection are largely independent of TCR signaling. αPix(-) thymocytes also paused less during migration in the thymic cortex, interacted less with ICAM-1 coated beads, and could overcome TCR stop signals, consistent with defective scanning behavior. These results identify αPIX as a regulator of thymocyte migration and subsequent arrest that is linked to positive selection.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Timo
/
Movimiento Celular
/
Timocitos
/
Factores de Intercambio de Guanina Nucleótido Rho
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2014
Tipo del documento:
Article