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

Erdi, Balázs; Nagy, Péter; Zvara, Agnes; Varga, Agnes; Pircs, Karolina LU ; Ménesi, Dalma; Puskás, László G and Juhász, Gábor (2012) In Autophagy 8(7). p.35-1124
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Autophagy, Drosophila Proteins, Drosophila melanogaster, Fat Body, Gene Knockdown Techniques, Genes, Insect, Glycogen, Larva, Oligonucleotide Array Sequence Analysis, Protein Transport, Receptors, Cytoplasmic and Nuclear, Transcription, Genetic, Journal Article, Research Support, Non-U.S. Gov't
in
Autophagy
volume
8
issue
7
pages
12 pages
publisher
Landes Bioscience
external identifiers
  • scopus:84866102456
ISSN
1554-8635
DOI
10.4161/auto.20069
language
English
LU publication?
no
id
ca06da0f-9cba-4fe4-926c-3047f29a131e
date added to LUP
2017-03-16 15:27:48
date last changed
2017-10-01 05:32:10
@article{ca06da0f-9cba-4fe4-926c-3047f29a131e,
  abstract     = {<p>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.</p>},
  author       = {Erdi, Balázs and Nagy, Péter and Zvara, Agnes and Varga, Agnes and Pircs, Karolina and Ménesi, Dalma and Puskás, László G and Juhász, Gábor},
  issn         = {1554-8635},
  keyword      = {Animals,Autophagy,Drosophila Proteins,Drosophila melanogaster,Fat Body,Gene Knockdown Techniques,Genes, Insect,Glycogen,Larva,Oligonucleotide Array Sequence Analysis,Protein Transport,Receptors, Cytoplasmic and Nuclear,Transcription, Genetic,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {07},
  number       = {7},
  pages        = {35--1124},
  publisher    = {Landes Bioscience},
  series       = {Autophagy},
  title        = {Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila},
  url          = {http://dx.doi.org/10.4161/auto.20069},
  volume       = {8},
  year         = {2012},
}