Ca2+ Regulates Cofilin Nuclear Translocation through Distinct Mechanisms in Rat Basophilic Leukemia Cells.

Cofilin severs actin filaments and translocates to the nucleus. Though Ser3 dephosphorylation of cofilin is required for its actin-depolymerization activity, the mechanism regulating cofilin's nuclear translocation remains unclear. In rat basophilic leukemia (RBL-2H3) cells, we previously reported that the transient Ser3 dephosphorylation in cofilin plays a role in actin polymerization/depolymerization after multivalent antigen stimulation. In this study, we revealed that multivalent antigen stimulation rapidly induced the nuclear localization of cofilin within 1 min. Ser3 dephosphorylation and cofilin's nuclear localization were elicited by ionomycin addition, while pretreatment with BAPTA-AM inhibited the nuclear translocation of cofilin according to multivalent antigen stimulation, suggesting that the increase in intracellular Ca2+ concentration ([Ca2+]i) is essential for the nuclear translocation of cofilin. Meanwhile, the dephosphorylation at Ser3 and nuclear localization of cofilin occurred in the absence of extracellular Ca2+ without multivalent antigen stimulation. Interestingly, the constitutively inactive form of cofilin (Ser3 to glutamic acid) was translocated to the nucleus following multivalent antigen stimulation, but not following extracellular Ca2+ depletion. These findings indicate that the increase in [Ca2+]i induced by multivalent antigen triggers the nuclear translocation of cofilin independent of Ser3 dephosphorylation, while extracellular Ca2+ depletion-induced nuclear translocation of cofilin depends on Ser3 dephosphorylation. This suggests that distinct pathways regulate the nuclear translocation of cofilin based on Ca2+ dependency.