Fig. 8

Function of UNC93B1 and STIM1 in Ca²⁺ influx and antigen cross-presentation in DCs. In WT DCs, UNC93B1 associates with STIM1 through their ER-facing domains resulting in STIM1 oligomerization and activation. In DCs carrying the 3d mutation, UNC93B1-STIM1 association is compromised leading to decreased STIM1 oligomerization and activation, and to reduced SOCE and periphagosomal Ca²⁺ signaling. UNC93B1 participates to events critical for efficient cross-presentation either STIM1 dependent (antigen degradation, phago-lysosomal fusion, phagosomal Ca²⁺ hotspots, in red in the scheme) or STIM1 independent (endosomal/phagosomal pH, NOX2 recruitment and ROS production, cathepsins activity and antigen export to the cytosol, TLR folding and transport, highlighted in black). In 3d/3d cells, all these parameters are severely impaired resulting in inefficient antigen cross-presentation. In summary, UNC93B1, together with STIM1, are important regulators of antigen cross-presentation by modulating phagosomal homeostasis and calcium physiology in DCs. Ag: antigen, CysC: cystatin C, LRO: lysosome-related organelle