RISE IN NUCLEAR CALCIUM TRANSLOCATES ANNEXIN-IV AND ANNEXIN-V TO THE NUCLEAR-ENVELOPE

Following incubation of human fibroblasts with Ca2+ ionophore A23187, we found strong immunofluorescence labelling of the nuclear envelope b y annexin IV antibody. Using confocal imaging of cells loaded with Flu o-3, we showed that A23187 generates an intense and sustained rise of Ca2+ in the nucleus, By contrast, stimulation without extracellular Ca 2+ produces only a brief rise in nuclear Ca2+ that does not promote an nexin IV translocation to the nuclear envelope, and compounds that ind uce only a transient increase of nuclear Ca2+ do not support transloca tion of annexin IV. In addition, annexin V was also translocated to th e nuclear envelope by A23187, but distribution of annexins I, II, VI a nd VII is unaffected, In in vitro assays with isolated nuclei, annexin V was also found to bind to the nuclear envelope in a Ca (2+)-depende nt manner, These results demonstrate that the translocation to the nuc lear envelope of different types of Ca2+-regulated proteins is directl y triggered by a major rise of Ca2+ in the nucleus.