Fas ligand interacting proteins : new insights into complex signaling networks
The Fas ligand is a death factor and a potential signal transducer. Here we show the retrograde signaling of FasL could be demonstrated in human T cells. FasL engagement results in a severe block of T cell activation without increased cell death. In cytotoxic T cells, NK cells , FasL can be located intracellularly in 'secretory lysosomes' and delivered to the immunological synapse upon eg. TCR stimulation. The proline-rich domain (PRD) in the cytosolic portion of FasL is required to prevent direct surface expression of the molecule. With FCH/SH3 family of closely related proteins, it was demonstrated members of this family can interact with FasL and changed the subcellular localization of FasL when co-expressed in non-hematopoietic cells indicating a major role of these interactors in guiding FasL to the lysosomal compartment. The observation that the adapter protein Nck1 co-localizes with the FasL in the area of target cell contact suggested that the TCR-triggered recruitment of Nck1 might result in a directed transport of FasL and associated secretory lysosomes into the forming immunological synapse.