Wijesekera, T.P., Stephens, N.P., Hingnekar, A., Gedamu, H.Y., Dezso, N.R., Strange, M., Risbud, S.M., Dinh, A.D., Atkinson, N.S. (2025). The non-nuclear DifB NF-κB isoform affects courtship, circadian, and locomotor behavior in adult Drosophila melanogaster.  Front. Behav. Neurosci. 19(): 1689016.

FBrf0264180

Research paper

The Drosophila Dif gene uses alternative messenger RNA (mRNA) processing to encode two different nuclear factor kappa Bs (NF-κBs). The DifA isoform is a canonical NF-κB transcription factor that is important for activation of the immune response. Our primary interest is the DifB isoform, which is neuron-specific and expressed in the mushroom bodies and antennal lobes of the adult brain. The DifB protein lacks a nuclear localization signal and does not enter the nucleus. Instead, it localizes to the cell body surrounding the nucleus, to axonal-dendritic projections, and to the synapse. DifB is an unusual member of the NF-κB superfamily, as it acts outside the nucleus to modulate behavior. The DifB isoform has been shown to modulate the sensitivity of the adult to sedation by alcohol. Here, we conducted a survey to determine whether the DifB NF-κB is important for other fly behaviors. We observed that a DifB-specific mutation strongly suppresses male courtship. However, despite the expression of DifB in the mushroom bodies, a DifB null allele does not interfere with learning in a learned-suppression-of-phototaxis assay. Finally, both DifA-specific and DifB-specific mutations caused flies to have a circadian long rhythm phenotype, although the circadian phenotype cannot be scored in male DifB mutants because of a sexually dimorphic locomotor defect.

PMC12727931 (PMC) (EuropePMC)