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Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila

Érdi, Balázs and Nagy, Péter and Zvara, Ágnes and Varga, Ágnes and Pircs, Karolina and Ménesi, Dalma and Puskás, László G. and Juhász, Gábor (2012) Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila. Autophagy, 8 (7). pp. 1124-1135. ISSN 1554-8627

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: antimicrobial peptides, Atg8, autophagy, Drosophila, fat body, glycogen, GSK-3B, microarray, Rack1, starvation
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
Depositing User: Kata Berkes
Date Deposited: 10 Sep 2014 09:30
Last Modified: 10 Sep 2014 09:30
URI: http://real.mtak.hu/id/eprint/14604

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