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 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.
Groves
Benjamin
B
Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
Abrahamsen
Hilde
H
Clingan
Heather
H
Frantz
Michael
M
Mavor
Lauren
L
Bailey
Jeffrey
J
Ma
Dzwokai
D
D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D055786:Gene Knockout Techniques; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D002352:Carrier Proteins; C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases