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

Abstract

AbstractT 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 the 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.