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

Balázs Érdi, Péter Nagy, A. Zvara, Ágnes Varga, Karolina Pircs, Dalma Ménesi, L. Puskás, G. Juhász

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1124-1135
Number of pages12
JournalAutophagy
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Autophagy
Starvation
Glycogen
Drosophila
Genes
Glycogen Synthase Kinases
Food
Fat Body
Eukaryotic Cells
S cerevisiae ASC1 protein
DNA Replication
Cell Adhesion
Cell Movement
Larva
Cell Survival
Genotype
Genome
Neoplasms
Proteins

Keywords

  • Antimicrobial peptides
  • Atg8
  • Autophagy
  • Drosophila
  • Fat body
  • Glycogen
  • GSK-3B
  • Microarray
  • Rack1
  • Starvation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila. / Érdi, Balázs; Nagy, Péter; Zvara, A.; Varga, Ágnes; Pircs, Karolina; Ménesi, Dalma; Puskás, L.; Juhász, G.

In: Autophagy, Vol. 8, No. 7, 07.2012, p. 1124-1135.

Research output: Contribution to journalArticle

Érdi, Balázs ; Nagy, Péter ; Zvara, A. ; Varga, Ágnes ; Pircs, Karolina ; Ménesi, Dalma ; Puskás, L. ; Juhász, G. / Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila. In: Autophagy. 2012 ; Vol. 8, No. 7. pp. 1124-1135.
@article{f32287c4148f4f3ebfcf639f4d26fba2,
title = "Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila",
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.",
keywords = "Antimicrobial peptides, Atg8, Autophagy, Drosophila, Fat body, Glycogen, GSK-3B, Microarray, Rack1, Starvation",
author = "Bal{\'a}zs {\'E}rdi and P{\'e}ter Nagy and A. Zvara and {\'A}gnes Varga and Karolina Pircs and Dalma M{\'e}nesi and L. Pusk{\'a}s and G. Juh{\'a}sz",
year = "2012",
month = "7",
doi = "10.4161/auto.20069",
language = "English",
volume = "8",
pages = "1124--1135",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "7",

}

TY - JOUR

T1 - Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila

AU - Érdi, Balázs

AU - Nagy, Péter

AU - Zvara, A.

AU - Varga, Ágnes

AU - Pircs, Karolina

AU - Ménesi, Dalma

AU - Puskás, L.

AU - Juhász, G.

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - Antimicrobial peptides

KW - Atg8

KW - Autophagy

KW - Drosophila

KW - Fat body

KW - Glycogen

KW - GSK-3B

KW - Microarray

KW - Rack1

KW - Starvation

UR - http://www.scopus.com/inward/record.url?scp=84866102456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866102456&partnerID=8YFLogxK

U2 - 10.4161/auto.20069

DO - 10.4161/auto.20069

M3 - Article

VL - 8

SP - 1124

EP - 1135

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 7

ER -