Role of stress responses in regulating photoreceptor structural plasticity

摘要

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.