Retrograde transport of transcription factor NF-kappa B in living neurons.
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.
Wellmann
H
H
Institut für Neurobiochemie, Universität Witten/Herdecke, Stockumer Strasse 10, D-58448 Witten, Germany.
Kaltschmidt
B
B
Kaltschmidt
C
C
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D017931:DNA Primers; D008164:Luminescent Proteins; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases; D007608:Kainic Acid