AMPK activates the Nrf2-Keap1 pathway to govern dendrite pruning via the insulin pathway in Drosophila.

Autor:	Yuh Chew L; Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore.; Department of Biological Sciences, National University of Singapore, 117543, Singapore., He J; Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore., Wong JJL; Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore., Li S; Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou 510631, China., Yu F; Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore.; Department of Biological Sciences, National University of Singapore, 117543, Singapore.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2022 Jul 15; Vol. 149 (14). Date of Electronic Publication: 2022 Jul 14.
DOI:	10.1242/dev.200536
Abstrakt:	During Drosophila metamorphosis, the ddaC dendritic arborisation sensory neurons selectively prune their larval dendrites in response to steroid hormone ecdysone signalling. The Nrf2-Keap1 pathway acts downstream of ecdysone signalling to promote proteasomal degradation and thereby dendrite pruning. However, how the Nrf2-Keap1 pathway is activated remains largely unclear. Here, we demonstrate that the metabolic regulator AMP-activated protein kinase (AMPK) plays a cell-autonomous role in dendrite pruning. Importantly, AMPK is required for Mical and Headcase expression and for activation of the Nrf2-Keap1 pathway. We reveal that AMPK promotes the Nrf2-Keap1 pathway and dendrite pruning partly via inhibition of the insulin pathway. Moreover, the AMPK-insulin pathway is required for ecdysone signalling to activate the Nrf2-Keap1 pathway during dendrite pruning. Overall, this study reveals an important mechanism whereby ecdysone signalling activates the Nrf2-Keap1 pathway via the AMPK-insulin pathway to promote dendrite pruning, and further suggests that during the nonfeeding prepupal stage metabolic alterations lead to activation of the Nrf2-Keap1 pathway and dendrite pruning. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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