著者

Hinata Kawamura Satoko Hakeda-Suzuki Takashi Suzuki

出版者

The Genetics Society of Japan

雑誌

Genes & Genetic Systems (ISSN:13417568)

巻号頁・発行日

vol.95, no.5, pp.235-247, 2020-10-01 (Released:2021-02-11)

参考文献数

49

被引用文献数

6

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Neural activity contributes to synaptic regulation in sensory systems, which allows organisms to adjust to changing environments. However, little is known about how synaptic molecular components are regulated to achieve activity-dependent plasticity at central synapses. Previous studies have shown that following prolonged exposure to natural ambient light, the presynaptic active zone (AZ), an area associated with presynaptic neurotransmitter release in Drosophila photoreceptors, undergoes reversible remodeling. Other studies suggest that the secretory protein Wingless (Wg; an ortholog of Wnt-1) can mediate communication between synaptic cells to achieve synaptic remodeling. However, the source of Wg and the mechanism of Wg signal modulation by neuronal activity remained unclear. Here, we found that Wg secreted from glial cells regulates synaptic remodeling in photoreceptors. In addition, antibody staining revealed that Wg changes its localization depending on light conditions. Although Wg is secreted from glial cells, Wg appeared inside photoreceptor axons when flies were kept under light conditions, suggesting that an increase in neuronal activity causes Wg internalization into photoreceptors by endocytosis. Indeed, by blocking endocytosis in photoreceptors, the localization of Wg in photoreceptors disappeared. Interestingly, Wg accumulation was higher in axons with disassembled AZ structure than in axons whose AZ structure was stabilized at the single-cell level, indicating that Wg endocytosis may trigger AZ disassembly. Furthermore, when we genetically activated Wg signaling, Wg accumulation in photoreceptors decreased. Conversely, when we suppressed Wg signaling there was an increase in Wg accumulation. Through RNAi screening of Ca2+-binding proteins in photoreceptors, we found that Calcineurin is a key molecule that triggers Wg endocytosis. Overall, we propose that Wg signaling is regulated by a negative feedback loop driven by Wg endocytosis. The increase in neuronal activity is transmitted via calcium signaling, which leads to a decrease in Wg signaling and thereby promotes presynaptic remodeling.

著者

Tomohiro Araki Jiro Osaka Yuya Kato Mai Shimozono Hinata Kawamura Riku Iwanaga Satoko Hakeda-Suzuki Takashi Suzuki

出版者

The Genetics Society of Japan

雑誌

Genes & Genetic Systems (ISSN:13417568)

巻号頁・発行日

pp.19-00066, (Released:2020-06-04)

参考文献数

25

被引用文献数

3

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In many animals, neural activity contributes to the adaptive refinement of synaptic properties, such as firing frequency and the number of synapses, for learning, memorizing and adapting for survival. However, the molecular mechanisms underlying such activity-dependent synaptic remodeling remain largely unknown. In the synapses of Drosophila melanogaster, the presynaptic active zone (AZ) forms a T-shaped presynaptic density comprising AZ proteins, including Bruchpilot (Brp). In a previous study, we found that the signal from a fusion protein molecular marker consisting of Brp and mCherry becomes diffuse under continuous light over three days (LL), reflecting disassembly of the AZ, while remaining punctate under continuous darkness. To identify the molecular players controlling this synaptic remodeling, we used the fusion protein molecular marker and performed RNAi screening against 208 neuron-related transmembrane genes that are highly expressed in the Drosophila visual system. Second analyses using the STaR (synaptic tagging with recombination) technique, which showed a decrease in synapse number under the LL condition, and subsequent mutant and overexpression analysis confirmed that five genes are involved in the activity-dependent AZ disassembly. This work demonstrates the feasibility of identifying genes involved in activity-dependent synaptic remodeling in Drosophila, and also provides unexpected insight into the molecular mechanisms involved in cholesterol metabolism and biosynthesis of the insect molting hormone ecdysone.