Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 2932 |
| Journal | Nature communications |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Funding
The authors thank Drs. Dean Smith, Adrian Rothenfluh, Daisuke Hattori and members of the Krämer and Tagliabracci labs for helpful comments to the manuscript and technical assistance. We are grateful for Zuhair Zaidi for the initial setup of ethoscopes, Dr. Quentin Geissmann for advice on ethoscope data analysis, Dr. Byeongha Jeong for his generous help in 3D printing and solving software issues related to ethoscope, and Dr. Shin Yamazaki for kind help in analyzing circadian rhythm data. We thank Dr. Bhaskar Thakur for his kind help in the statistical analysis of data. We thank Dr. Hyung Don Ryoo and the Bloomington Drosophila Stock Center (NIH P40OD018537) for flies, the Molecular and Cellular Imaging Facility at the University of Texas Southwestern Medical Center for help with electron microscopy (NIH S10 OD020103-01). We thank Drs. Hyung Don Ryoo and Joseph M. Bateman, and the Developmental Studies Hybridoma Bank at The University of Iowa for antibodies. This work was funded by NIH grants R01EY010199, R01EY033184 and 5R01AI155426 to H.K. and NIH grant DP2 OD027405 and Welch Foundation Grant I-1911 to V.S.T. The authors thank Drs. Dean Smith, Adrian Rothenfluh, Daisuke Hattori and members of the Krämer and Tagliabracci labs for helpful comments to the manuscript and technical assistance. We are grateful for Zuhair Zaidi for the initial setup of ethoscopes, Dr. Quentin Geissmann for advice on ethoscope data analysis, Dr. Byeongha Jeong for his generous help in 3D printing and solving software issues related to ethoscope, and Dr. Shin Yamazaki for kind help in analyzing circadian rhythm data. We thank Dr. Bhaskar Thakur for his kind help in the statistical analysis of data. We thank Dr. Hyung Don Ryoo and the Bloomington Drosophila Stock Center (NIH P40OD018537) for flies, the Molecular and Cellular Imaging Facility at the University of Texas Southwestern Medical Center for help with electron microscopy (NIH S10 OD020103-01). We thank Drs. Hyung Don Ryoo and Joseph M. Bateman, and the Developmental Studies Hybridoma Bank at The University of Iowa for antibodies. This work was funded by NIH grants R01EY010199, R01EY033184 and 5R01AI155426 to H.K. and NIH grant DP2 OD027405 and Welch Foundation Grant I-1911 to V.S.T.
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy