Interplay between autophagy and CncC regulates dendrite pruning in Drosophila.
Proc Natl Acad Sci U S A
; 121(10): e2310740121, 2024 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-38408233
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Drosophila
/
Drosophila
/
Compostos de Amônio Quaternário
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Singapura