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.

RSK/GSK3–mediated phosphorylation of FilGAP regulates chemotactic cancer invasion

“…β-chimerin, a Rac-specific GAP, regulates T-cell adhesion and chemotaxis in a diacylglycerol-dependent manner ( 53 ). FilGAP inhibits cell polarization and motility evoked by Stromal cell-derived factor-1 in pro-B lymphocytes ( 54 ), suggesting that phosphorylation of FilGAP by RSK/GSK3 is also involved in lymphocyte chemotaxis.…”

Manifestation of Functional Defects of Nervous System in <i>Upf3</i> Mutants <i>Drosophila melanogaster</i> at Larval and Adult Stages

“…Additionally, this will also provide a target explanation in the neurodegenerative phenotypes noticed in the Upf3 mutants. In humans, the homolog Rho GTPase activating protein 24 (ARHGAP24) in addition to regulation of neuronal growth [29] regulates cell polarity, inhibits cell cycle progression and induces apoptosis in renal carcinoma [30,31]. Another factor that may partially contribute to the short life span in the Upf3 mutant adults is the Upf3 acquired role in telomere maintenance and DNA repair in both humans and Drosophila [4].…”

Regulation of Cell Morphology and Migration by a Rho GTPase Activating Protein FilGAP

“…Depletion of FilGAP in lymphocyte increased cell polarization and migration speed induced by SDF-1 (stromal cell-derived factor 1α) (Iida et al, 2016). SDF-1 stimulated FilGAP depleted lymphocytes show more persistent migration than control cells because of more stable lamellae formation.…”