CLASP1/2 regulate immune synapse maturation in natural killer cells

Abstract Natural killer (NK) cells are the first line of defense against viral infections and tumors. Their cytotoxic activity relies on the formation of an immune synapse (IS) with target cells. The lymphocyte function–associated antigen (LFA)-1 plays a central role in NK cell cytotoxicity by modulating NK-IS assembly and maturation. LFA-1 organization at the IS involves a Golgi-dependent mechanism that has not been fully elucidated. CLIP-associating proteins (CLASP) 1/2 are microtubule plus-tip interacting proteins that control the dynamics of Golgi-derived microtubules (GDMTs). In the present study, we found that CLASP1/2 depletion impaired LFA-1 organization at the IS and inhibited the polarization of the centrosome and the lytic granules toward the target cell, thereby compromising NK cytotoxic function. Our results also revealed the role of the Golgi apparatus as a microtubule-organizing center (MTOC) in these cells. Furthermore, we found that, similar to what was described in other cell types, NK cells require CLASP1/2 and AKAP350 for efficient nucleation of microtubules at the Golgi. Overall, this study uncovers the role of CLASP1/2 in the maturation of the lytic IS in NK cells and presents evidence supporting the contribution of GDMTs in this process.