Maintaining Toll signaling in Drosophila brain is required to sustain autophagy for dopamine neuron survival

Jie Zhang; Ting Tang; Ruonan Zhang; Liang Wen; Xiaojuan Deng; Xiaoxia Xu; Wanying Yang; Fengliang Jin; Yang Cao; Yuzhen Lu; Xiao-Qiang Yu

doi:10.1016/j.isci.2024.108795

Maintaining Toll signaling in Drosophila brain is required to sustain autophagy for dopamine neuron survival

iScience. 2024 Jan 4;27(2):108795. doi: 10.1016/j.isci.2024.108795. eCollection 2024 Feb 16.

Authors

Jie Zhang^{1

2}, Ting Tang¹, Ruonan Zhang^{1

2}, Liang Wen¹, Xiaojuan Deng³, Xiaoxia Xu², Wanying Yang³, Fengliang Jin², Yang Cao³, Yuzhen Lu¹, Xiao-Qiang Yu¹

Affiliations

¹ Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China.
² Key Laboratory of Bio-Pesticide Innovation and Application of Guangdong Province, College of Plant Protection, South China Agricultural University, Guangzhou 510642, Guangdong, China.
³ Guangdong Laboratory for Lingnan Modern Agriculture, Laboratory of Insect Molecular Biology and Biotechnology, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Abstract

Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.

Keywords: Cell biology; Neuroscience.