An inhibitory role of the G-protein regulator AGS3 in mTOR-dependent macroautophagy

Macroautophagy is a cellular process whereby the cell sequesters and recycles cytosolic constituents in a lysosome-dependent manner. It has also been implicated in a number of disorders, including cancer and neurodegeneration. Although a previous report that AGS3 over-expression promotes macroautoph...

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Bibliographic Details
Published inPloS one Vol. 5; no. 1; p. e8877
Main Authors Groves, Benjamin, Abrahamsen, Hilde, Clingan, Heather, Frantz, Michael, Mavor, Lauren, Bailey, Jeffrey, Ma, Dzwokai
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 26.01.2010
Public Library of Science (PLoS)
Subjects
Autophagy
Autophagy - physiology
Blotting, Western
Brain research
Cancer
Carrier Proteins - genetics
Carrier Proteins - physiology
Cell Biology
Cell Biology/Cellular Death and Stress Responses
Cell death
Cell Line
Colorectal cancer
Developmental biology
Electrophoresis, Polyacrylamide Gel
Gene Knockout Techniques
Guanine Nucleotide Dissociation Inhibitors
Humans
Immunoprecipitation
Intracellular Signaling Peptides and Proteins - physiology
Kinases
Localization
Medical research
Membranes
Metabolism
Molecular Biology
Mutagenesis, Site-Directed
Neurodegeneration
Neurosciences
Overexpression
Phosphorylation
Polymerase Chain Reaction
Protein-Serine-Threonine Kinases - physiology
Proteins
Rapamycin
Rodents
TOR protein
TOR Serine-Threonine Kinases
Whooping cough
Santa Barbara California
California
United States > US
Norway
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Summary:Macroautophagy is a cellular process whereby the cell sequesters and recycles cytosolic constituents in a lysosome-dependent manner. It has also been implicated in a number of disorders, including cancer and neurodegeneration. Although a previous report that AGS3 over-expression promotes macroautophagy suggests a stimulatory role of AGS3 in this process, we have found that knock-down of AGS3, unexpectedly, also induces macroautophagy, indicating an inhibitory function of endogenous AGS3 in macroautophagy. Interestingly, AGS3 phosphorylation is decreased upon induction of mammalian target of rapamycin (mTOR)-dependent macroautophagy. Moreover, unlike wild-type AGS3, over-expression of an AGS3 mutant lacking this modification fails to enhance macroautophagic activity. These observations imply that AGS3 phosphorylation may participate in the modulation of macroautophagy.
Bibliography:Conceived and designed the experiments: BBG HA DM. Performed the experiments: BBG HA HC MF LM JB. Analyzed the data: BBG HA DM. Wrote the paper: BBG DM.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0008877