In nervous systems, retrograde signals are key for organizing circuit activity and maintaining neuronal homeostasis. We identify the conserved Allnighter (Aln) pseudokinase as a cell non-autonomous regulator of proteostasis responses necessary for normal sleep and structural plasticity of Drosophila photoreceptors. In aln mutants exposed to extended ambient light, proteostasis is dysregulated and photoreceptors develop striking, but reversible, dysmorphology. The aln gene is widely expressed in different neurons, but not photoreceptors. However, secreted Aln protein is retrogradely endocytosed by photoreceptors. Inhibition of photoreceptor synaptic release reduces Aln levels in lamina neurons, consistent with secreted Aln acting in a feedback loop. In addition, aln mutants exhibit reduced night time sleep, providing a molecular link between dysregulated proteostasis and sleep, two characteristics of ageing and neurodegenerative diseases.

在神经系统中，逆行信号是组织回路活动和维持神经元稳态的关键。我们将保守的 Allnighter (Aln) 假激酶确定为果蝇光感受器正常睡眠和结构可塑性所必需的蛋白稳态反应的细胞非自主调节剂。在一些暴露于长时间环境光的突变体中，蛋白质稳态失调，光感受器出现显着但可逆的畸形。阿尔恩_基因在不同的神经元中广泛表达，但在光感受器中不表达。然而，分泌的 Aln 蛋白被光感受器逆行内吞。光感受器突触释放的抑制降低了层神经元中的 Aln 水平，这与在反馈回路中起作用的分泌的 Aln 一致。此外，aln突变体表现出夜间睡眠减少，提供蛋白质稳态失调与睡眠之间的分子联系，这是衰老和神经退行性疾病的两个特征。