A rise in nuclear calcium translocates annexins IV and V to the nuclear envelope.
Following incubation of human fibroblasts with Ca2+ ionophore A23187, we found strong immunofluorescence labelling of the nuclear envelope by annexin IV antibody. Using confocal imaging of cells loaded with Fluo-3, we showed that A23187 generates an intense and sustained rise of Ca2+ in the nucleus. By contrast, stimulation without extracellular Ca2+ produces only a brief rise in nuclear Ca2+ that does not promote annexin IV translocation to the nuclear envelope, and compounds that induce only a transient increase of nuclear Ca2+ do not support translocation of annexin IV. In addition, annexin V was also translocated to the nuclear envelope by A23187, but distribution of annexins I, II, VI and VII is unaffected. In in vitro assays with isolated nuclei, annexin V was also found to bind to the nuclear envelope in a Ca2+-dependent manner. These results demonstrate that the translocation to the nuclear envelope of different types of Ca2+-regulated proteins is directly triggered by a major rise of Ca2+ in the nucleus.
Raynal
P
P
Laboratory of Cell Biology and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kuijpers
G
G
Rojas
E
E
Pollard
H B
HB
D000818:Animals; D017314:Annexin A4 / Q000737:chemistry / Q000378:metabolism*; D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008856:Microscopy, Fluorescence / Q000379:methods; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism*; D010741:Phospholipases A / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D017314:Annexin A4; D017304:Annexin A5; D007476:Ionophores; D000001:Calcimycin; D010741:Phospholipases A; D001920:Bradykinin; D002118:Calcium