Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila
Autor: | László G. Puskás, Ágnes Varga, Dalma Ménesi, Péter Nagy, Gábor Juhász, Balázs Érdi, Ágnes Zvara, Karolina Pircs |
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Rok vydání: | 2012 |
Předmět: |
Resource
autophagy Atg1 Transcription Genetic ATG8 Fat Body Receptors Cytoplasmic and Nuclear Genes Insect Biology Receptors for Activated C Kinase antimicrobial peptides chemistry.chemical_compound GSK-3 GSK-3B Animals Drosophila Proteins Glycogen synthase Molecular Biology Protein kinase C Oligonucleotide Array Sequence Analysis 2. Zero hunger Glycogen Autophagy starvation Cell Biology Rack1 Cell biology Protein Transport Drosophila melanogaster Biochemistry chemistry glycogen Gene Knockdown Techniques Larva biology.protein Drosophila Atg8 microarray Drosophila Protein |
Zdroj: | Autophagy |
ISSN: | 1554-8635 1554-8627 |
Popis: | 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. |
Databáze: | OpenAIRE |
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