Toll signaling promotes JNK-dependent apoptosis in Drosophila

Zhuojie Li; Chenxi Wu; Xiang Ding; Wenzhe Li; Lei Xue

doi:10.1186/s13008-020-00062-5

Toll signaling promotes JNK-dependent apoptosis in Drosophila

Cell Div. 2020 Mar 10:15:7. doi: 10.1186/s13008-020-00062-5. eCollection 2020.

Authors

Zhuojie Li^#¹, Chenxi Wu^#^{1

2}, Xiang Ding¹, Wenzhe Li¹, Lei Xue^{1

3}

Affiliations

¹ 1Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092 China.
² 2College of Traditional Chinese Medicine, North China University of Science and Technology, 21 Bohai Road, Tangshan, 063210 China.
³ 3Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong 519000 China.

^# Contributed equally.

Abstract

Background: Apoptosis plays pivotal roles in organ development and tissue homeostasis, with its major function to remove unhealthy cells that may compromise the fitness of the organism. Toll signaling, with the ancient evolutionary origin, regulates embryonic dorsal-ventral patterning, axon targeting and degeneration, and innate immunity. Using Drosophila as a genetic model, we characterized the role of Toll signaling in apoptotic cell death.

Results: We found that gain of Toll signaling is able to trigger caspase-dependent cell death in development. In addition, JNK activity is required for Toll-induced cell death. Furthermore, ectopic Toll expression induces the activation of JNK pathway. Moreover, physiological activation of Toll signaling is sufficient to produce JNK-dependent cell death. Finally, Toll signaling activates JNK-mediated cell death through promoting ROS production.

Conclusions: As Toll pathway has been evolutionarily conserved from Drosophila to human, this study may shed light on the mechanism of mammalian Toll-like receptors (TLRs) signaling in apoptotic cell death.

Keywords: Cell death; Drosophila; JNK; ROS; Toll.