TRANSLOCATION OF CALMODULIN TO THE NUCLEUS SUPPORTS CREB PHOSPHORYLATION IN HIPPOCAMPAL-NEURONS

Activation of the transcription factor CREB is thought to be important in the formation of long-term memory in several animal species(1-3). The phosphorylation of a serine residue at position 133 of CREB is cri tical for activation of CREB4. This phosphorylation is rapid when driv en by brief synaptic activity in hippocampal neurons(5), It is initiat ed by a highly local, rise in calcium ion concentration(5) near the ce ll membrane, but culminates in the activation of a specific calmodulin -dependent kinase known as CaMK IV (ref. 7), which is constitutively p resent in the neuronal nucleus(7,8). It is unclear how the signal is c onveyed from the synapse to the nucleus, We show here that brief burst s of activity cause a swift (similar to 1 min) translocation of calmod ulin from the cytoplasm to the nucleus, and that this translocation is important for the rapid phosphorylation of CREB, Certain Ca2+ entry s ystems (L-type Ca2+ channels and NMDA receptors) are able to cause mob ilization of calmodulin, whereas others (N- and P/Q-type Ca2+ channels ) are not. This translocation of calmodulin provides a form of cellula r communication that combines the specificity of local Ca2+ signalling with the ability to produce action at a distance.