Protein kinase C δ regulates the clearance of actin at the immunological synapse required for polarized exosome secretion by T cells

Abstract

Multivesicular bodies (MVB) enclose intraluminal vesicles (ILV) formed by inward budding from the membrane of endosomes. In T lymphocytes, ILV are secreted as Fas ligand-bearing, pro-apoptotic exosomes following T cell receptor (TCR)-induced fusion of the MVB with the plasma membrane at the immune synapse (IS). Diacylglycerol (DAG) and DAG kinase α (DGKα) regulate the polarized traffic of MVB towards the IS in T lymphocytes and exosome secretion. We show that Protein Kinase Cδ (PKCδ) regulates TCR-controlled, MVB polarization towards the IS and exosome secretion. Concomitantly, we demonstrate defects in activation-induced cell death in PKCδ-interfered T lymphocytes. Spatiotemporal reorganization of actin at the IS is controlled by PKCδ. TCR-controlled phosphorylation of T538 residue of adaptor paxillin at the microtubule organizing centre (MTOC) is decreased in PKCδ-interfered cells. PKCδ-dependent actin reorganization at the IS is a key regulator of MVB polarized secretory traffic.