Hormone-induced secretory and nuclear translocation of calmodulin: Oscillations of calmodulin concentration with the nucleus as an integrator

Many important enzyme activities are regulated by Ca2+-dependent interactio ns with calmodulin (CaM), Some of the most important targets for CaM action are in the nucleus, and Ca2+-dependent CaM translocation into this organel le has been reported, Hormone-evoked cytosolic Ca2+ signals occur physiolog ically as oscillations, but, so far, oscillations in CaM concentration have not been described. We loaded fluorescent-labeled CaM into pancreatic acin ar cells and monitored the fluorescence in various regions by confocal micr oscopy. Sustained high concentrations of the hormone cholecystokinin or the neurotransmitter acetylcholine evoked a transient movement of cytosolic Ca M from the basal nonnuclear area into the secretory granule region and, the reafter, a more substantial and prolonged translocation of CaM into the nuc leoplasm About 50% of the CaM that bound Ca2+ translocated, At a lower horm one concentration, evoking Ca2+ oscillations, regular spikes of increased C aM concentration were seen in the secretory granule region with mirror imag e spikes of decreased CaM concentration in the basal nonnuclear region. The nucleus was able to integrate the Ca2+ spike-evoked pulses of CaM transloc ation into a sustained elevation of the nucleoplasmic concentration of this protein.