NF-kappa B activity is induced by neural cell adhesion molecule binding toneurons and astrocytes

The neural cell adhesion molecule, N-CAM, is expressed on the surface of as trocytes and neurons, and N-CAM hemophilic binding has been shown to alter gene expression in both of these cell types. To determine mechanisms by whi ch N-CAM regulates gene expression, we have analyzed DNA binding of and tra nscriptional activation by NF-kappa B after N-CAM binding to the cell surfa ce, Addition of purified N-CAM, the recombinant third immunoglobulin domain of N-CAM, or N-CAM antibodies either to neonatal rat forebrain astrocytes or to cerebellar granule neurons increased NF-kappa B/DNA binding activity in nuclear extracts as measured by electrophoretic mobility shift assays. A nalysis using supershifting antibodies indicated that, in both cell types, p50 and p65 but not p52, c-Rel, or Rel B were contained in the NF-kappa B-b inding complex. NF-kappa B-mediated transcription was increased after N-CAM binding to astrocytes and neurons as demonstrated by the activation of two different luciferase reporter constructs containing NF-kappa B-binding sit es. N-CAM binding also resulted in degradation of I kappa B-alpha protein f ollowed by an increase in the levels of I kappa B-alpha mRNA and protein. T hese results indicate that N-CAM hemophilic binding at the cell membrane le ads to increased NF-kappa B binding to DNA and transcriptional activation i n both neurons and astrocytes. Activation of NF-kappa B, however, did not i nfluence the previously reported ability of N-CAM to inhibit astrocyte prol iferation. These observations together support the hypothesis that N-CAM bi nding activates multiple pathways leading to changes in gene expression in both astrocytes and neurons.