The RacGAP protein FilGAP is a negative regulator of chemokine-promoted lymphocyte migration

Abstract

Rho family small GTPases regulate lymphocyte migration induced by chemokines. However, how lymphocyte migration is regulated by Rho GTPases remains to be elucidated. Here, we identified FilGAP, a Rac-specific GAP, as a negative regulator of lymphocyte polarization and migration. Depletion of FilGAP in mouse pro-B BAF cells increased cellular elongation and membrane protrusion after stimulation of the cells with SDF-1α, which caused increased migration speed. Although FilGAP is detectable both at the front and rear of polarized cells, FilGAP appears to be concentrated at the tip of retracting lamellae of moving lymphocytes. Moreover, depletion of FilGAP increased activation of Rac at the front of polarized cells. Thus, FilGAP may inhibit lamellae extension at the front of moving lymphocytes. Depletion of Rac GAP protein, FilGAP, increased cell polarization and elongation of BAF lymphocytic cells upon stimulation with cytokine SDF-1α. Depletion of FilGAP increased migration speed of BAF cells. FilGAP is localized at the tip of the retracting lamella of moving BAF cells. FilGAP may inhibit Rac at the front of moving BAF cells to antagonize PI3 kinase-dependent activation of Rac.