AKAP350 regulates LFA-1 organization during NK cytolytic response

Natural killer (NK) cell cytotoxicity requires extensive cytoskeleton remodeling and membrane receptor reorganization at the NK-target cell immune synapse (IS). The lymphocyte function associated antigen (LFA) 1 accumulates at that structure, playing a central role in NK-IS assembly. The mechanisms underlying LFA-1 accumulation at the IS remain unclear. We found that AKAP350, a centrosome/Golgi associated protein, enabled NK-cytolytic activity by facilitating LFA-1 organization at the IS. Our results revealed the existence of an intracellular pool of LFA-1 that colocalized with the Golgi apparatus, which redistributed to the IS pole in control, but not in cells with decreased expression or localization of AKAP350 at the Golgi apparatus. Similarly to what was described in other cells, our results showed that NK cells nucleated microtubules at the Golgi apparatus in an AKAP350-dependent manner. Concomitantly, AKAP350 delocalization from the Golgi apparatus or pharmacological disruption of microtubule dynamics or Golgi integrity impaired LFA-1 localization at the IS. Altogether, our results unveil a novel mechanism of LFA-1 reorganization relevant for NK-cell activation, revealing the participation of the Golgi apparatus in NK-lytic IS maturation.