The mechanism by which signals such as those produced by glutamate are transferred to the nucleus may involve direct transport of an activated transcription factor to trigger long-term transcriptional changes. Ionotropic glutamate 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 fluorescent protein. We found that green fluorescent protein-RelA was located in either the nucleus or cytoplasm and neurites, depending on the coexpression of the cognate inhibitor of NF-kappaB, IkappaB-alpha. Stimulation with glutamate, kainate, or potassium chloride resulted in a redistribution of NF-kappaB from neurites to the nucleus. This transport depended on an intact nuclear localization signal on RelA. Thus, in addition to its role as a transcription factor, NF-kappaB may be a signal transducer, transmitting transient glutamatergic signals from distant sites to the nucleus.