期刊
AUTOPHAGY
卷 8, 期 7, 页码 1124-1135出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.20069
关键词
antimicrobial peptides; Atg8; autophagy; Drosophila; fat body; glycogen; GSK-3B; microarray; Rack1; starvation
类别
资金
- Wellcome Trust [087518/Z/08/Z]
- Hungarian Scientific Research Fund [OTKA PD72095]
- Hungarian Academy of Sciences [BO/00712/07, BO/00781/11, BO/00552/11]
- European Union
- European Social Fund [TAMOP 4.2.1./B-09/1/KMR-2010-0003]
- Wellcome Trust [087518/Z/08/Z] Funding Source: Wellcome Trust
Autophagy delivers cytoplasmic material for lysosomal degradation in eukaryotic cells. Starvation induces high levels of autophagy to promote survival in the lack of nutrients. We compared genome-wide transcriptional profiles of fed and starved control, autophagy-deficient Atg7 and Atg1 null mutant Drosophila larvae to search for novel regulators of autophagy. Genes involved in catabolic processes including autophagy were transcriptionally upregulated in all cases. We also detected repression of genes involved in DNA replication in autophagy mutants compared with control animals. The expression of Rack1 (receptor of activated protein kinase C 1) increased 4.1- to 5.5-fold during nutrient deprivation in all three genotypes. The scaffold protein Rack1 plays a role in a wide range of processes including translation, cell adhesion and migration, cell survival and cancer. Loss of Rack1 led to attenuated autophagic response to starvation, and glycogen stores were decreased 11.8-fold in Rack1 mutant cells. Endogenous Rack1 partially colocalized with GFP-Atg8a and early autophagic structures on the ultrastructural level, suggesting its involvement in autophagosome formation. Endogenous Rack1 also showed a high degree of colocalization with glycogen particles in the larval fat body, and with Shaggy, the Drosophila homolog of glycogen synthase kinase 3B (GSK-3B). Our results, for the first time, demonstrated the fundamental role of Rack1 in autophagy and glycogen synthesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据