Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis

Calreticulin and calnexin are Ca2+-binding proteins with chaperone activity in the endoplasmic reticulum. These proteins have been eliminated by gene replacement in Dictyostelium, the only microorganism known to harbor both p roteins; family members in Dictyostelium are located at the base of phyloge netic trees. A dramatic decline in the rate of phagocytosis was observed in double mutants lacking calreticulin and calnexin, whereas only mild change s occurred in single mutants. Dictyostelium cells are professional phagocyt es, capable of internalizing particles by a sequence of activities: adhesio n of the particle to the cell surface, actin-dependent outgrowth of a phago cytic cup, and separation of the phagosome from the plasma membrane. In the double-null mutants, particles still adhered to the cell surface, but the outgrowth of phagocytic cups was compromised. Green fluorescent protein-tag ged calreticulin and calnexin, expressed in wild-type cells, revealed a dir ect link of the endoplasmic reticulum to the phagocytic cup enclosing a par ticle, such that the Ca2+ storage capacity of calreticulin and calnexin mig ht directly modulate activities of the actin system during particle uptake.