A protein kinase A-regulated centrosomal actin pool sets the threshold for T cell polarization

Abstract

T lymphocyte migration triggered by chemokine stimulation is preceded by cell polarization. The acquisition of this asymmetry requires a profound cell rearrangement, particularly of the cytoskeleton. The mechanism by which a uniform signal triggered by chemokine receptors rapidly leads to this asymmetry is largely elusive. Using cell imaging, we emphasize that the centrosome dictates the position of the polarization axis in T lymphocytes. Mechanistically, we highlight that the T cell shape is controlled by the amount of actin filaments surrounding the centrosome. In resting conditions as well as after chemokine stimulation, the activity of a specific pool of protein kinase A regulates this cytoskeleton compartment. Once the centrosomal actin is reduced below a certain threshold, the symmetry breaking is catalyzed. This study points to a critical protein kinase A signaling pathway in the establishment of the immune response.