AUTHOR=Wijesekera Thilini P. , Stephens Nicole P. , Hingnekar Aniket , Gedamu Hanna Y. , Dezso Natalie R. , Strange Madison , Risbud Saee M. , Dinh Alexander D. , Atkinson Nigel S. 

TITLE=The non-nuclear DifB NF-κB isoform affects courtship, circadian, and locomotor behavior in adult Drosophila melanogaster

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2025.1689016

DOI=10.3389/fnbeh.2025.1689016

ISSN=1662-5153

ABSTRACT=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.