Abstract

Cell polarity is required for the functional specialization of many cell types including lymphocytes. A hallmark of cell polarity is the reorientation of the centrosome that allows repositioning of organelles and vesicles in an asymmetric fashion. The mechanisms underlying centrosome polarization are not fully understood. Here we found that in resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which is needed for centrosome tethering to the nucleus via the LINC complex. Upon lymphocyte activation, Arp2/3 is partially depleted from the centrosome as a result of its recruitment to the immune synapse. This leads to a reduction in F-actin nucleation at the centrosome and thereby allows its detachment from the nucleus and polarization to the synapse. Therefore, F-actin nucleation at the centrosome—regulated by the availability of the Arp2/3 complex—determines its capacity to polarize in response to external stimuli.

Highlights

  • Cell polarity is required for the functional specialization of many cell types including lymphocytes

  • Centrosome polarization in these cells can be triggered by engaging their membrane antigen receptor—the B-cell antigen receptor (BCR)—with surface-tethered ligands coated on latex beads (Fig. 1a), planar surfaces or cells[14,17,22]

  • Genome ontology (GO) term enrichment was performed on these 835 proteins

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Summary

Introduction

Cell polarity is required for the functional specialization of many cell types including lymphocytes. Arp2/3 is partially depleted from the centrosome as a result of its recruitment to the immune synapse This leads to a reduction in F-actin nucleation at the centrosome and thereby allows its detachment from the nucleus and polarization to the synapse. The term immune synapse refers to the zone of tight interaction that forms between lymphocytes and antigen-presenting cells towards which the centrosome polarizes[9]. It is viewed as a signalling platform where both exocytotic and endocytotic events needed for lymphocytes to perform their specific effector function take place[10]. F-actin nucleation at the centrosome determines the ability of this organelle to polarize to one cell pole

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