The mechanism by which signals such as those produced by glutamate are tran
sferred to the nucleus may involve direct transport of an activated transcr
iption factor to trigger long-term transcriptional changes. Ionotropic glut
amate receptor activation or depolarization activates transcription factor
NF-kappaB and leads to translocation of NF-kappaB from the cytoplasm to the
nucleus. We investigated the dynamics of NF-kappaB translocation in living
neurons by tracing the NF-kappaB subunit RelA (p65) with jellyfish green f
luorescent protein. We found that green fluorescent protein-RelA was locate
d in either the nucleus or cytoplasm and neurites, depending on the coexpre
ssion of the cognate inhibitor of NF-kappaB, I kappaB-alpha. Stimulation wi
th glutamate, kainate, or potassium chloride resulted in a redistribution o
f NF-kappaB from neurites to the nucleus. This transport depended on an int
act nuclear localization signal on RelA. Thus, in addition to its role as a
transcription factor, NF-kappaB may be a signal transducer, transmitting t
ransient glutamatergic signals from distant sites to the nucleus.