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

FEBS Lett. 2016 May;590(10):1395-408. doi: 10.1002/1873-3468.12189. Epub 2016 May 11.

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.

Keywords: Rac; Rho; cell adhesion; cell migration; cell polarity; chemotaxis; signal transduction; small GTPases.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Polarity
  • Chemokine CXCL12 / metabolism*
  • Chemotaxis*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Lymphocytes / cytology*
  • Lymphocytes / metabolism
  • Mice
  • rac GTP-Binding Proteins / metabolism

Substances

  • ARHGAP24 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • GTPase-Activating Proteins
  • rac GTP-Binding Proteins