| First Author | Korthals M | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 7 | Pages | 3228-38 |
| PubMed ID | 24591366 | Mgi Jnum | J:209876 |
| Mgi Id | MGI:5568864 | Doi | 10.4049/jimmunol.1302585 |
| Citation | Korthals M, et al. (2014) alphaPIX RhoGEF supports positive selection by restraining migration and promoting arrest of thymocytes. J Immunol 192(7):3228-38 |
| abstractText | 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 alpha-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. alphaPIX was also required for efficient positive selection, but not negative selection, of thymocytes. TCR signaling was normal in alphaPix(-) thymocytes, indicating that the effects of alphaPIX on positive selection are largely independent of TCR signaling. alphaPix(-) 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 alphaPIX as a regulator of thymocyte migration and subsequent arrest that is linked to positive selection. |
