Interplay between autophagy and CncC regulates dendrite pruning in Drosophila

• 成果类型: Article
• 署名作者: Tan, Jue Yu Kelly; Chew, Liang Yuh; Juhasz, Gabor; Yu, Fengwei
• 署名单位: National University of Singapore; National University of Singapore; Eotvos Lorand University; HUN-REN; HUN-REN Biological Research Center; Institute of Genetics - HAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15193
• DOI: 10.1073/pnas.2310740121
• 发表日期: 2024-03-01
• 关键词: transcription factor nrf2; central-nervous-system; programmed cell-death; proteasomal degradation; axon; metamorphosis; mechanisms; protein; p62; phosphorylation

摘要

Autophagy is essential for the turnover of damaged organelles and long - lived proteins. It is responsible for many biological processes such as maintaining brain functions and aging. Impaired autophagy is often linked to neurodevelopmental and neurodegenerative diseases in humans. However, the role of autophagy in neuronal pruning during development remains poorly understood. Here, we report that autophagy regulates dendrite- specific pruning of ddaC sensory neurons in parallel to local caspase activation. Impaired autophagy causes the formation of ubiquitinated protein aggregates in ddaC neurons, dependent on the autophagic receptor Ref(2)P. Furthermore, the metabolic regulator AMP- activated protein kinase and the insulin-target of rapamycin pathway act upstream to regulate autophagy during dendrite pruning. Importantly, autophagy is required to activate the transcription factor CncC (Cap n collar isoform C), thereby promoting dendrite pruning. Conversely, CncC also indirectly affects autophagic activity via proteasomal degradation, as impaired CncC results in the inhibition of autophagy through sequestration of Atg8a into ubiquitinated protein aggregates. Thus, this study demonstrates the important role of autophagy in activating CncC prior to dendrite pruning, and further reveals an interplay between autophagy and CncC in neuronal pruning.