Abstract
Neuronal systems must adapt to fast and slow changes in the environment. A classic example is
the visual system which can adjust to changes in several orders of magnitude in light levels
within just seconds. Adaptation has also been observed on a much longer time scale, such as
seasonal changes in the light period. In Drosophila, shifts to an extended light period trigger a
reduction in the size of rhabdomeres, the light-sensitive organelle of photoreceptors, and a
down regulation of their synaptic active zones. We recently discovered that regulation of this
structural plasticity depends on the unfolded protein response (UPR). After just one night with
continued light exposure, both the IreI and the PERK arm of the UPR are activated. Interference
with the normal regulation of the UPR results in the loss of visual neurotransmission and severe
structural deterioration of rhabdomeres, the microvillar arrays that house the key elements of
the phototransduction cascade. This phenotype was observed for fic and BiP mutants that
interfere with the regulation of the activity of BiP, a major regulator of the UPR. Screening for
additional elements of this pathway, we identified an unconventional kinase-like protein, called
Allnighter, as a candidate. Its sequence predict that this protein may be a kinase acting in the
secretory pathway. Preliminary data indicate that, similar to fic and BiP mutants, an extended
light period causes allnighter mutants to lose visual neurotransmission and structural integrity
of rhabdomeres. This proposal aims to characterize the mechanisms regulating photoreceptor
structural plasticity and the specific role of Allnighter in this process. Specifically, we will test
how regulation of two key stress pathways, the unfolded proteins response and autophagy,
contributes to structural plasticity and the mechanisms by which the Allnighter protein modifies
both of these pathways. Completion of these experiments will significantly enhance our
understanding of the mechanism that drive structural plasticity of photoreceptors and maintain
visual acuity during long-term adaptation.