View Program - 63rd Annual Drosophila Research Conference

NF-κB proteins are well known as transcription factors important in immune system activation. In this highly conserved role, they contribute to changes in behavior in response to infection and in response to a variety of other insults and experiences. In some mammalian neurons, NF-κBs can be found at the synapse and translocate to the nucleus when activated by synaptic activity. In these areas, NF-κBs are believed to produce change by acting in the nucleus to alter gene expression. Here we demonstrate that in Drosophila melanogaster, NF-κB action is important both inside and outside the nucleus and that the Dif gene has segregated nuclear and non-nuclear NF-κB action into different protein isoforms. The DifA isoform is a canonical nuclear-acting NF-κB protein that enters the nucleus and is centrally important for combating infection. The DifB variant, but not the DifA variant, is expressed in central nervous system neurons. DifB does not enter the nucleus and co-localizes with a synaptic protein. Mutations specific to DifB alter alcohol behavioral sensitivity but have no obvious effect on combating infection, whereas DifA mutants do not affect alcohol sensitivity but compromise the capacity to combat infection. These data are evidence that the unusual, non-nuclear DifB variant, alters behavior by a synaptic mechanism that is local and nongenomic and that diverges from the canonical NF-κB transcriptional effects used in the peripheral immune system. The Drosophila DifB variant is an ideal system for studying non-nuclear NF-κB effects in isolation from NF-κB action in the nucleus.

A non-nuclear NF-κB modulates behavioral alcohol sensitivity but not immunity